Method of forming articles including waveguides via capillary micromolding and microtransfer molding

ABSTRACT

Chemically or biochemically active agents or other species are patterned on a substrate surface by providing a micromold having a contoured surface and forming, on a substrate surface, a chemically or biochemically active agent or fluid precursor of a structure. A chemically or biochemically active agent or fluid precursor also can be transferred from indentations in an applicator to a substrate surface. The substrate surface can be planar or non-planar. Fluid precursors of polymeric structures, inorganic ceramics and salts, and the like can be used to form patterned polymeric articles, inorganic salts and ceramics, reactive ion etch masks, etc. at the surface. The articles can be formed in a pattern including a portion having a lateral dimension of less than about 1 millimeter or smaller. The indentation pattern of the applicator can be used to transfer separate, distinct chemically or biochemically active agents or fluid precursors to separate, isolated regions of a substrate surface. Waveguide arrays, combinatorial chemical or biochemical libraries, etc. can be made. Differences in refractive index of waveguide and cladding can be created by subjecting the waveguide and cladding, made of identical prepolymeric material, to different polymerization or cross-linking conditions. Interferometers are defined by coupling arrays of waveguides, where coupling can be controlled by altering the difference in refractive index between cladding and waveguide at any desired location of the array. Alteration and refractive index can be created photochemically, chemically, or the like. Sensors also are disclosed, including biochemical sensors.

RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 09/004,583, filed Jan. 8, 1998 now U.S. Pat. No. 6,355,198 which isa continuation-in-part of U.S. application Ser. No. 08/616,929 by EnochKim et al. entitled “Method of Forming Articles and Patterning Surfacesvia Capillary Micromolding”, filed Mar. 15, 1996 now abandoned, Ser. No.09/004,583 is also a continuation-in-part of U.S. provisionalapplication serial No. 60/046,689 by Xiao-Mei Zhao et al. entitled“Molded Waveguides and Waveguide Couplers”, filed May 16, 1997, each ofwhich is incorporated herein by reference.

STATEMENT AS TO POTENTIAL RIGHTS UNDER FEDERALLY SPONSORED RESEARCH ANDDEVELOPMENT

Research leading to the invention disclosed and claimed herein wassupported in part by the Office of Naval Research, ONR Contract No.N00014-93-I-0498, and by the National Science Foundation, NSF Grant No.PHY 9312572. The U.S. Government may have certain rights to theinvention.

FIELD OF THE INVENTION

The present invention relates generally to microprocesses at surfaces,and more particularly to the formation of micropatterned articles suchas waveguides, sensors, and switches on substrates from fluidprecursors, and mechanisms for micro-scale positioning of biologicallyactive agents at predetermined regions of a surface.

BACKGROUND OF THE INVENTION

In the fields of chemistry, biology, materials science,microelectronics, and optics, the development of devices that are smallrelative to the state of the art and conveniently and relativelyinexpensively reproduced is important.

A well-known method of production of devices, especially in the area ofmicroelectronics, is photolithography. According to this technique, anegative or positive resist (photoresist) is coated onto an exposedsurface of an article. The resist then is irradiated in a predeterminedpattern, and portions of the resist that are irradiated (positiveresist) or nonirradiated (negative resist) are removed from the surfaceto produce a predetermined pattern of resist on the surface, This isfollowed by one or more procedures.

According to one, the resist may serve as a mask in an etching processin which areas of the material not covered by the resist are chemicallyremoved, followed by removal of resist to expose a predetermined patternof a conducting, insulating, or semiconducting material. According toanother, the patterned surface is exposed to a plating medium or tometal deposition (for example under vacuum) followed by removal ofresist, resulting in a predetermined plated pattern on the surface ofthe material. In addition to photolithography, x-ray and electron-beamlithography have found analogous use.

In an article entitled “Materials for Optical Data Storage”, byEmmelius, et al., Angewandte Chemie, Int. Ed. (English), 28, 11,1445-1600 (November, 1989), a review of methods of making CD/ROM, WORM,and EDRAW optical storage disks is presented. According to one method,photolithography is used to create a pattern of protrusions on a surfacethat can serve as a master for fabrication of articles that have asurface including a series of ridges and protrusions complementary tothe photolithographically-produced master. These articles, includingmicroridges and grooves at one surface, can be combined with othermaterials in a layered structure to form an optical storage device. Anarticle in the Phillips Technical Review, volume 40, number 10 (1982),entitled “Manufacture of LaserVision Video Disks by aPhotopolymerization Process”, by Haverkorn, et al., discusses similartechnology. U.S. Pat. Nos. 5,170,461 (Yoon, et al.), 4,959,252(Bonnebat, et al.) and 5,141,785 (Yoshinada, et al.) describe opticalelements such as waveguides and optical recording media. Yoshinada, etal. describe a process involving coating a substrate with a polymer orprepolymer, pressing a contoured stamp into the polymer or prepolymer tocreate a contoured pattern in a surface of the polymer or prepolymercomplementary to the contoured surface of the stamp, removing the stamp,and adding a reflective layer to the contoured surface of the polymer orprepolymer for use as an optical device.

Photolithographic techniques for fabricating surfaces with positionalcontrol of chemical functionalities at submicron resolution is describedin an article entitled “Patterning of Self-Assembled Films UsingLithographic Exposure Tools”, by Dressick, et al., Jpn. J Appl. Phys.,32, 5829-5839 (December, 1993). The technique involves exposure of aself-assembled film to deep UV irradiation through a mask. According toone technique, photochemical cleavage of an organic group occurs inexposed regions followed by chemical reactivity selectively at thoseregions.

Photolithography has found application in the biological arena as well.Sundberg, et al. describe a method for patterning receptors, antibodies,and other macromolecules at precise locations on solid substrates usingphotolithographic techniques in combination with avidin orstreptavidin/biotin interaction in an article entitled“Spatially-Addressable Immobilization of Macromolecules on SolidSupports”, J Am. Chem. Soc., 117, 12050-12057 (1995).

Reactive ion etching is a process that is useful in the semiconductorindustry and other arenas for forming very small structures having avery high aspect ratio (a very high height/width ratio of features).Reactive ion etching is a dry process in which a gas is acceleratedtowards a surface to effect etching, in contrast to wet etchingprocesses in which a liquid is simply allowed to contact certain regionsof a surface and to chemically react at those regions. In wet etchingprocesses, etching typically takes place not only in a directionperpendicular to the surface, but horizontally, as well. That is, withwet etching it can be difficult to etch relatively precise, verticalchannels in a surface. Instead, the sidewalls of the channel are etchedhorizontally also. Reactive ion etching provides an advantageousalternative for etching channels with good, near-vertical sidewalls.

Reactive ion etching masks should have certain characteristics such asgood hardness, inertness to the etchent species, and in many caseselectrical insulating properties. Thus, materials suitable for reactiveion etching masks are limited. Many metal masks, such as gold masks, areunsuitable since the metals can sputter easily. Polymeric maskstypically degrade under reactive ion etching conditions. A typical priorart reactive ion etching mask is made of silica and is formed bycreating a layer of silica on a surface and etching the layerselectively to create a silica mask, using photolithography. Suchprocedures can be costly. In an article entitled “Poly(siloxane)-basedChemically Amplified Resist Convertable into Silica Glass”, by Ito, etal., Jpn. J Appl Phys., 32, 6052-6058 (1993), a poly(siloxane)-basedchemically amplified resist is reported. A polymeric glass precursor isconverted into silicate glass through a lithographic procedure.

Waveguides are generally defined by a core, surrounded by a cladding,that acts as a guide of electromagnetic radiation. The waveguide canpropagate radiation via total internal reflection of the radiationwithin the core. Waveguides have served as important components ofsensors and switches, and have been fabricated from a variety ofmaterials including inorganic materials such as glasses and organicmaterials such as polymers. Polymeric waveguides have been fabricatedusing reactive ion etching, ultraviolet (UV) laser and electron-beamwriting, induced dopant diffusion during polymerization (photo-lockingand selective polymerization), selective poling of electro-opticallyactive molecules induced by an electric field, and polymerization ofself-assembled prepolymers. One common technique for forming polymericwaveguides is injection molding. For example, voids in a claddingmaterial (or substrate) can be filled, via injection molding, with acore material. However, problems associated with this technique includesoftening and deformation of the cladding or substrate undertemperatures required for injection molding. Fabrication with precisionis compromised, typically. In an additional prior art technique, apolymeric film is spun onto a substrate and portions of the film aresubsequently exposed to light by a photolithographic process, therebychanging the refractive index of a polymeric film and creating awaveguide in the film. This technique requires expensive and complicatedphotolithographic systems for base formation of the waveguide array, andsubsequent multi-step processing is required such as removal of thepolymeric film from the substrate, lamination processing, curingprocessing, and other processing steps.

U.S. Pat. No. 5,136,678 (Yoshimura) describe fabrication of an opticalwaveguide array by providing a clad substrate having a number of groovesarranged in lines on a surface of the substrate, the substrate beingresistant to a UV-curable resin. A UV-curable resin is used to fill thegrooves in the substrate and is UV cured to form a core material, and acovering clad portion is formed over the structure of a material that isthe same as or close to the material used as the substrate “cladding”.

U.S. Pat. No. 5,313,545 (Kuo, et al.) describes a technique in which atwo-part mold made of stainless steel, aluminum, ceramic, or the like isused to mold a polymeric waveguide core material via injection molding.The mold is opened via removal of the two portions, and the waveguide isplaced in a second mold into which is injected a cladding material. Kuo,et al. report that a post-mold curing process is sometimes needed tomaximize optical and physical qualities of core regions, supportapparatus, and end portions.

U.S. Pat. No. 5,390,275 (Lebby, et al.) describe a method formanufacturing a molded waveguide. A first cladding layer is provided,and channels are formed in the first cladding layer. The channels in thefirst cladding layer are filled with an optically transparent polymer,and a second cladding layer is subsequently affixed over the channelsthereby enclosing them.

U.S. Pat. No. 5,481,633 (Mayer) describes vertical coupling structuresin which waveguide patterns include sections that lie in close proximitywith other sections, for example one directly above another, such thatthe distance between coupling portions is very small and couplingbetween different guides can occur.

Biological and chemical interactions can be studied on the micro scaleusing combinatorial chemistry. This technique, as described in Chemical& Engineering News, 74, 7, 28-73 (Feb. 12, 1996), involves formation ofdifferent biological or chemical species in a grid pattern on a surfaceand used, for example, to screen compounds for potential biological orchemical activity. An article entitled “CombinatorialChemistry-Applications of Light-Directed Chemical Synthesis”, by Jacobs,et al., Trends in Biotechnology, 12, 19-26 (January, 1994) describes aphotolithographic process used in a spatially-addressable synthesistechnique for forming a combinatorial library involvingphotolithography. A surface is derivatized with amine linkers that areblocked by a photochemically cleavable protecting group. The surface isselectively irradiated to liberate free amines that can be coupled tophotochemically blocked building blocks. The process is repeated withdifferent regions of the surface being exposed to light and involved insynthesis until a desired array of different compounds, in a gridpattern on the surface, is prepared. Each of these compounds then isassayed simultaneously for binding or activity. Binding “hits” can beidentified by the particular location at which binding on the surfaceoccurs.

While the above techniques represent, in some cases, useful advances inthe art, many of these techniques require relatively sophisticatedapparatus, are expensive, and generally consume more reactants andproduce more by-products in collateral fabrication steps than isoptimal, and/or lack optimal versatility in application. It is an objectof the present invention to provide a variety of techniques formodifying a surface chemically and/or biologically at the micro andnanoscale, and to form very small scale structures, including waveguidesand masks for etching processes conveniently, inexpensively, andreproducibly.

SUMMARY OF THE INVENTION

The present invention provides techniques for derivatizing surfaces,biologically, chemically, or physically, according to predeterminedpatterns. The derivatized surfaces find a variety of uses in a varietyof technical areas, or a structure formed on the surface can be removedfrom the surface and find utility separate from the surface. Theinvention involves, according to one technique, a method for creating apattern of a species at a defined region proximate a substrate surface.The method involves providing an article having a contoured surfaceincluding at least one indentation defining a pattern and forming at afirst region proximate the substrate surface, in a pattern correspondingto the indentation pattern, a fluid precursor of the species. The fluidprecursor is allowed to harden at the first region of the substratesurface in a pattern corresponding to the indentation pattern and in anarea including a portion having a lateral dimension of less than about 1mm. A second region proximate the substrate surface, contiguous with thefirst region, remains free of the species.

The invention also provides a method of promoting a chemical reaction ata defined region proximate a substrate surface. The method involvespositioning an article proximate a substrate surface and applying, to afirst region proximate the substrate surface via capillary actioninvolving the article, a chemically active agent. A chemical reactioninvolving the chemically active agent then is allowed to take place atthe first region proximate the substrate surface.

The invention also provides a method of promoting a chemical reaction ata defined region proximate a substrate surface that involves providingan article having a contoured surface including at least one indentationdefining a pattern, forming at a first region proximate the substratesurface, in a pattern corresponding to the indentation pattern, achemically active agent, and allowing a chemical reaction to take placeproximate the first region of the substrate surface. The chemicalreaction takes place in a pattern corresponding to the indentationpattern and in an area including a portion having a lateral dimension ofless than about 1 mm. A second region proximate the substrate surface,contiguous with the first region, remains free of the reaction.

The invention also provides a method of applying a biochemically activeagent to a region proximate a substrate surface. An article having acontoured surface, as described above, is used to form, at a firstregion proximate the substrate surface and in a pattern corresponding tothe indentation pattern, a pattern of the biochemically active agent.The method can further involve allowing a biochemical interactioninvolving the biochemically active agent to take place proximate thefirst region of the substrate surface in a pattern corresponding to theindentation pattern. The first region can be defined by an area having alateral dimension of less than about 1 mm, and a second region proximatethe substrate surface, contiguous with the first region, can be leftfree of the biochemical interaction. The biochemically active agent canbe a biological binding partner that can be used in subsequent bindingwith other agents.

The invention also provides a method of creating a pattern of a speciesproximate a substrate surface that includes positioning a formingarticle proximate a substrate surface and applying, to a first regionproximate the substrate surface via capillary action involving thearticle, a fluid precursor of the species. The fluid precursor isallowed to harden and the forming article is removed from the substratesurface.

The invention also provides a method of promoting a chemical reaction ata defined region proximate a substrate surface. The method involvestransferring a chemically active agent from an applicator having acontoured surface including at least one indentation defining anapplication pattern to a first region proximate a substrate surface in apattern corresponding to the indentation pattern. A second regionproximate the surface, contiguous with the first region, is allowed toremain free of the chemically active agent. A chemical reactioninvolving the chemically active agent can take place at the firstregion.

The invention also provides a method of promoting a biochemicalinteraction at a defined region proximate a substrate surface thatinvolves transferring a biochemically active agent from an applicatorhaving a contoured surface including at least one indentation definingan application pattern to a first region proximate a substrate surfacein a pattern corresponding to the application pattern. A second regionproximate the surface, contiguous with the first region, can remain freeof the biochemically active agent. A biochemical interaction involvingthe biochemically active agent can be allowed to take place at the firstregion.

The invention also provides a method of applying to a substrate surfacea biochemically active agent that involves positioning an articleproximate a substrate surface and applying, to a first region proximatethe substrate surface via capillary action involving the article, abiochemically active agent. A biochemical interaction involving thebiochemically active agent is allowed to take place at the first region.

The invention also provides a method for applying essentiallyinstantaneously to a first and a second region proximate a substratesurface separated from each other by an intervening region, distinctfirst and second chemically active agents, respectively. The interveningregion is left essentially free of the chemically active agent. Themethod can involve allowing a chemical reaction involving at least onechemically active agent to subsequently take place proximate the firstor second region. The method also can involve applying essentiallyinstantaneously to the first and second regions distinct first andsecond biochemically active agents while leaving the intervening regionfree of the biochemically active agent.

The invention also provides a method involving applying essentiallyinstantaneously to a first and a second region proximate a substratesurface distinct first and second biochemically active agents,respectively. The first and second regions are separated from each otherby an intervening region that remains free of biochemically activeagent. The method can be carried out as well with first and secondbiochemically active agents that are the same.

The invention also provides a method involving applying a first reactantto a first region proximate a surface and allowing a first reaction totake place at the first region. A second reactant then is applied to asecond region proximate the surface that is different from the firstregion but that includes a portion intersecting the first region. Thefirst region is blocked except at the intersecting region during thisstep, thereby preventing the first reactant from contacting the firstregion except at the intersecting portion. A second reaction is allowedto take place at the second region, thereby creating a first chemicalcharacteristic at the first region except at the intersecting portion, asecond chemical characteristic at the second region except at theintersecting portion, and a third chemical characteristic at theintersecting portion.

The invention also provides a method of establishing a first chemicalfunctionality at a first region proximate a substrate surface and adifferent chemical functionality at a second region proximate thesubstrate surface contiguous with the first region. The method involvesapplying to the first region proximate the substrate surface adeprotecting species to chemically deprotect the first region of thesubstrate surface and thereby render it chemically reactive, whileleaving the second region free of deprotection. Alternatively, thetechnique can involve transferring to the second region of the substratesurface a chemical protecting species. The method further involvesexposing the substrate surface to a chemically or biochemically reactivespecies that reacts at the first region proximate the substrate surfaceand does not react at the second region. The technique can be used tocreate a combinatorial library via a series of deprotecting/reacting,re-protecting steps or protecting/reacting/deprotecting steps. Transferof protecting or deprotecting species to the surface can take placeessentially instantaneously.

The invention also provides a method of creating, on a substratesurface, a patterned, self-assembled monolayer, involving transferring aself-assembled monolayer-forming species from an applicator having acontoured surface including at least one indentation defining anapplication pattern to a first region proximate the substrate surface. Aself-assembled monolayer proximate the first region is thereby formedcorresponding to the indentation pattern. A second region proximate thesurface, contiguous with the first region, remains free of theself-assembled monolayer.

The invention also provides a method involving providing a surfacecarrying a plurality of chelating agents distributed evenly thereacrossand applying to two discrete regions of the surface a metal ion that iscoordinated by the chelating agent, while leaving a region interveningthe two discrete regions free of the metal ion, thereby creating twodiscrete regions carrying chelating agents coordinating metal ions.

The invention also provides a method involving providing a surfacecarrying an essentially even distribution thereacross of chelatingagents coordinating metal ions, and applying to two discrete regions atthe surface a biologically active agent, while leaving a regionintervening the two discrete regions free of the biologically activeagent.

The invention also provides an article defined by a substrate having asurface and a self-assembled monolayer on the surface. The monolayer isformed of at least a first species having a formula X-R-Ch-M, wherein Xrepresents a functional group and R represents a spacer moiety that,together, are able to promote formation at the surface of aself-assembled monolayer. Ch represents a chelating agent thatcoordinates a metal ion. M represents a metal ion coordinated to thechelating agent. The article further includes a pattern of biologicalagent coordinated to metal ion at a first region proximate the surface.A second region proximate the surface, contiguous with the first region,remains free of biological agent coordinated to metal ion.

The invention also provides a method of creating a patterned,self-assembled monolayer on a substrate surface. The method involvestransferring a self-assembled monolayer-forming species from anapplicator having a contoured surface including at least one indentationdefining an application pattern to a first region proximate a substratesurface. A self-assembled monolayer is thereby formed proximate thefirst region of the substrate surface corresponding to the indentationpattern. A second region proximate the surface, contiguous with thefirst region, is left free of self-assembled monolayer. Theself-assembled monolayer can be transferred essentially instantaneouslyto the first region proximate the substrate surface in this manner.

The invention also provides a method for providing a surface carrying aplurality of chelating agents distributed evenly thereacross andapplying to two discrete regions at the surface a metal ion that iscoordinated by the chelating agent. A region intervening the twodiscrete regions is left free of metal ion.

The invention also provides a method involving providing a surface thatcarries, essentially evenly distributed thereacross, chelating agentscoordinating metal ions. A biochemically active agent is applied to twodiscrete regions at the surface and a region intervening the twodiscrete regions remains free of the biochemically active agent.

The invention also provides an article including a surface and a pathwayproximate the surface delineating a pattern at a first region proximatethe surface. The pattern includes at least one region defining acontinuous essentially linear portion of product formed proximate thesurface. The product is formed in this manner via reaction involving achemically active agent promoting the reaction that had been transferredproximate the surface from an applicator. The linear portion of theproduct has a dimension parallel to the surface of less than about onemillimeter.

The invention also provides an article as described above, where thepattern is defined by a plurality of microbeads assembled at thesurface. Any patterns formed in this manner can have at least onesection having a dimension parallel to the surface of less than aboutone millimeter.

The fluid precursors, chemically active agents, biochemically activeagents, and carriers can be any of a variety of species includingprepolymeric species, biological binding partners, inorganic salts,ceramics, metals, catalysts, colloidal activating agents, and the like.

A variety of combinations of the above-described inventive methods canbe carried out, for example formation of a pattern can be carried outvia capillary action, instantaneous transfer can take place to form apattern on a surface having a lateral dimension of less than about 1 mm,and the like. Articles formed by the methods above, or by anycombination of these methods, and articles formed by other methods areincluded. The methods can be carried out on essentially planar ornon-planar surfaces.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates schematically an arrangement for derivatizing asurface in a predetermined pattern according to one embodiment of theinvention;

FIG. 2 is a schematic illustration of a technique for transferring achemically or biochemically active agent or fluid precursor of anarticle from essentially linear indentations of an applicator definingan indentation pattern to a substrate surface in a pattern correspondingto the indentation pattern;

FIGS. 3a-3 d are photocopies of scanning electron micrographs (SEMs) ofpatterned polymeric structures formed from hardenable fluid precursorsin which the patterned structures remain at the surface (FIGS. 3a-c) orare removed from the surface to form a free-standing structure (FIG.3d);

FIGS. 4a-4 h are photocopies of SEM images of inorganic and organicmicrostructures patterned on surfaces in accordance with the invention;

FIG. 5 is a photocopy of an electron micrograph of microspheresassembled in a predetermined pattern proximate a substrate surface froma fluid precursor in accordance with the invention;

FIGS. 6a-6 c are photocopies of SEM images of metallic microstructuresformed proximate predetermined regions of a substrate surface inaccordance with the invention;

FIGS. 7a-7 c are photocopies of SEM images of a substrate surfacederivatized in a pattern with resist followed by lithography to etch thesubstrate surface in a pattern complementary to the resist pattern;

FIG. 8 illustrates schematically the formation of a free-standingarticle from a fluid precursor, using a substrate surface and a formingarticle including a pattern of indentations in accordance with theinvention;

FIGS. 9a-9 d are photocopies of SEM images of a free-standing articleprepared in accordance with the technique schematically illustrated inFIG. 8 and use of that article as a mask adjacent a substrate surface invapor deposition of metal (FIG. 9b) or creation of a secondary resistformed by a self-assembled monolayer deposited in a patterncomplementary to that of the mask, followed by removal of the mask andvapor deposition of metal in a pattern complementary to the secondaryresist pattern (FIGS. 9c-d);

FIGS. 10a-10 c illustrate schematically (FIG. 10a), and viaphotoreproduction of optical micrographs (FIG. 10b, c), a processinvolving derivatizing a surface with resist via micromolding, a mask soproduced, and a substrate surface etched selectively at regions notcovered by the mask;

FIG. 11 illustrates schematically a technique for transfer of achemically or biochemically active agent or a fluid precursor of anarticle from an applicator having a discontinuous indentation pattern toregions proximate a substrate surface in a pattern corresponding to theindentation pattern;

FIG. 12 illustrates schematically the transfer, from an articleincluding an indentation pattern, of a chemically or biochemicallyactive agent or other fluid species to a nonplanar substrate surface ina pattern corresponding to the indentation pattern;

FIG. 13 illustrates schematically a multi-layered article formed usingsuccessive micromolding techniques of the invention that can serve as awaveguide, and is a cross-section through line a—a of FIG. 15;

FIGS. 14a-14 k illustrate schematically the creation of a combinatoriallibrary in accordance with the invention;

FIG. 15 illustrates schematically several techniques of the inventionfor forming a waveguide array or other structure, from a fluidprecursor, on a substrate surface followed by formation of a claddinglayer over the waveguide array;

FIG. 16 illustrates a technique for forming a multi-layer waveguidestructure;

FIG. 17 is a schematic illustration of one type of prior art waveguidecoupler;

FIG. 18 is a schematic illustration of another type of prior artwaveguide coupler, namely an evanescent coupler;

FIG. 19 is a schematic illustration of a coupling region, switch, orsensor using a waveguide array of the present invention;

FIG. 20 illustrates formation of an interference pattern via couplingamong a five-waveguide array in accordance with the invention;

FIG. 21 is a photocopy of a scanning electron micrograph (SEM) image ofan unclad array fabricated in accordance with the invention;

FIG. 22 is a photocopy of an SEM image of a clad array fabricated inaccordance with the invention;

FIG. 23 is a schematic illustration of an optical system used to couplelight into waveguide arrays of the invention and to determineinterference patterns formed via coupling among the waveguides of thearrays;

FIGS. 24a-24 g show a variety of waveguide arrays and interferencepatterns of light emerging from various waveguide arrays and created viacoupling between waveguides of the arrays;

FIG. 25 illustrates schematically another technique of the invention forforming a structure from a precursor, on a substrate surface;

FIG. 26 is a photocopy of a SEM image of an aluminosilicate structurethat can serve as a waveguide;

FIG. 27 is a photocopy of a SEM image of a borosilicate structure thatcan serve as a waveguide; and

FIG. 28 is a photocopy of a SEM image of the structure of FIG. 27 at adifferent stage of annealing.

DETAILED DESCRIPTION OF THE INVENTION

U.S. patent application Ser. No. 08/616,692, filed Mar. 15, 1996,entitled “Microcontact Printing of Catalytic Colloids” by Hidber, etal., U.S. Provisional Patent Appln. S.No. 60/046,689, filed May 16,1997, entitled “Molded Waveguides and Waveguide Couplers”, by Kim, etal., and U.S. patent application Ser. No. 08/616,929, filed Mar. 15,1996 by Kim, et al., entitled “Method of Forming Articles and PatterningSurfaces via Capillary Micromolding” both are incorporated herein byreference in their entirety.

The present invention provides, in one aspect, techniques for placement,at regions proximate a substrate surface, of chemically or biochemicallyactive agents, fluid precursors of articles such as waveguides to beimmobilized proximate a substrate surface, and/or other speciesdesirably transferred to a region or regions proximate a substratesurface in a pattern. “Fluid precursor”, as used herein, means amaterial that is fluid enough that it can be formed into a pattern usinga forming article, using techniques described herein. The inventionutilizes an applicator having a pattern of indentations that can be usedto transfer such a species from the indentations to a region proximatethe substrate surface or that can serve as a mold that when, positionedproximate a substrate surface, can define a region in which such aspecies is positioned. In one set of preferred embodiments theapplicator is used to transfer a fluid precursor from the indentationsto a region proximate a substrate surface where the precursor ishardened to the point it is self-supporting and the applicator can beremoved. “Self-supporting, in this context, means that the precursordoes not lose its form unacceptably upon removal of the forming articleand can retain its form during a further hardening procedure.Alternatively, the applicator can be used to transfer a fluid precursorto a substrate surface and the applicator can be removed prior tohardening the fluid, but maintaining the fluid within channels definedbetween indentations in the contoured applicator surface and thesubstrate surface until the fluid is hardened is preferred, since theultimate shape of features of the pattern on the substrate is therebybetter-controlled.

FIG. 1 illustrates schematically a technique for derivatizing asubstrate surface according to a pattern of, for example, a polymericarticle, a pattern of microbeads optionally carrying a chemical orbiochemically active species, a catalyst or other activating agent forpromoting a chemical reaction such as metal plating at the surface, afluid carrying a dissolved or suspended species to be deposited orprecipitated, or the like. For purposes of illustration, the procedureschematically illustrated in FIG. 1 will be described with respect to ahardenable prepolymeric fluid that is hardened at the surface to form apatterned polymeric article. An article 20 includes an applicationsurface 22 having formed therein a plurality of indentations 24 thattogether define a linear, patterned array of indentations 24 that arecontiguous with a contact surface 26. Article 20, according to oneembodiment, is an applicator used to transfer a species, in a pattern,to a region or regions proximate the substrate surface, or a formingarticle or micromold placed proximate a substrate surface and used toguide a fluid species so as to position the species in a pattern at apredetermined region or regions proximate the substrate surface. As usedherein, the term “proximate” is meant to define at a substrate surface,that is, in contact with a substrate surface, or at a position near asubstrate surface and fixed relative to the substrate surface. Forexample, if a substrate surface carries an adhesion promoter, forexample a self-assembled monolayer, activity at the surface of theself-assembled monolayer is intended to mean activity proximate thesubstrate surface. When forming article 20 is placed proximate a surface28 of a substrate 30, contact surface 26 of the article seals portionsof surface 28 that it contacts, thereby forming channels 32 defined byindentations 24 and portions 34 of substrate surface 28 not contacted bycontact surface 26. In this manner a micromold is created, which isdefined by article 20 and substrate surface 28.

A fluid 36 that, according to the embodiment illustrated, is a precursorof a patterned, polymeric structure (but can be one of a variety ofspecies such as a carrier of a chemically or biochemically active agent,etc., as described herein) is placed adjacent one or more openings ofchannels 32 and introduced into the channels and allowed to flowadjacent portions 34 of substrate surface 28 in register withindentations 24. Fluid precursor 36 can be urged to flow via, forexample, pressure applied to the fluid as it is positioned so as toenter the channels, or vacuum created within the channels by, forexample, connection of the outlets of the channels to a source ofvacuum. Alternatively, according to one aspect of the invention, thefluid can be allowed to flow into the mold via capillary action.Capillary filling of the mold is especially useful when the mold is ofvery small dimension (in particular in the micro scale) and is definedherein to mean that when a fluid precursor is positioned adjacent anopening or channel 32 formed by a portion 34 of the substrate surfaceand an indentation 24 of article 20, the fluid precursor will flow intoat least a portion of the channel spontaneously.

Subsequent to introduction of the fluid precursor into the mold definedby channels 32, the fluid precursor can be hardened before or afterremoval of applicator 20 from substrate surface 28 (or where the fluidis a carrier of a species to be deposited or precipitated, the fluid candissipate, i.e., evaporate, be absorbed into applicator 20, or thelike). Where the fluid is viscous enough, or is allowed to reach aparticular level of viscosity, the applicator can be removed and theprecursor hardened at the surface without unacceptable loss ofdimensional integrity. In particularly preferred embodiments, the fluidprecursor is hardened to the extent that it is self-supporting(dimensionally-stable) prior to removal of Article 20 from the substratesurface.

According to one embodiment, the fluid precursor is a solution ofmonomer in a fluid carrier and is polymerized at the surface witharticle 20 in place. Article 20 then is removed. A structural article38, in a pattern corresponding to the indentation or mold pattern 24 ofarticle 20, results on substrate surface 28 from the describedprocedure. According to the description of the process illustrated inFIG. 1, structure 38 is a polymeric structure formed from a fluidprepolymeric precursor.

Where the structure 38 formed according to this embodiment is apolymeric structure, it can be thermally polymerized on substratesurface 28 via application of heat to the substrate and/or article 20or, if article 20 is removed prior to polymerization, via convective orradiative heat; photopolymerized if substrate 30 and/or article 20 aretransparent to radiation, or subsequent to removal of article 20.Free-radical polymerization can be carried out as well. These and otherforms of polymerization are known to those of ordinary skill in the artand can be applied to the techniques of the present invention withoutundue experimentation. All types of polymerization, including cationic,anionic, copolymerization, chain copolymerization, cross-linking, andthe like can be employed, and essentially any type of polymer orcopolymer formable from a fluid precursor can be patterned on surface 28in accordance with the invention. An exemplary, non-limiting list ofpolymers that are suitable include polyurethane, polyamides,polycarbonates, polyacetylenes and polydiacetylenes, polyphosphazenes,polysiloxanes, polyolefins, polyesters, polyethers, poly(ether ketones),poly(alkylene oxides), poly(ethylene terephthalate), poly(methylmethacrylate), polystyrene, and derivatives and block, random, radial,linear, or teleblock copolymers, cross-linkable materials such asproteinaceous material and/or blends of the above. Gels are suitablewhere dimensionally stable enough to maintain structural integrity uponremoval of article 20 from substrate surface 28. Also suitable arepolymers formed from monomeric alkyl acrylates, alkyl methacrylates,alpha-methylstyrene, vinyl chloride and other halogen-containingmonomers, maleic anhydride, acrylic acid, acrylonitrile, specifically,methyl methacrylate, imides, carbonates, hexafluoroisopropylmethacrylate, acrylonitrile, bromophenyl acrylates or bromophenylmethacrylates, and the like. Monomers can be used alone, or mixtures ofdifferent monomers can be used to form homopolymers and copolymers.Non-linear and ferroelectric polymers can be advantageous. Gels aresuitable where dimensionally stable enough to maintain structuralintegrity upon removal of article 20 from substrate surface 28. Theparticular polymer, copolymer, blend, or gel selected is not critical tothe invention, and those of skill in the art can tailor a particularmaterial for any of a wide variety of applications. The particularpolymer, copolymer, blend, or gel selected is not critical to theinvention, and those of skill in the art can tailor a particularmaterial for any of a wide variety of applications.

According to one embodiment, a polymerizable or cross-linkable species(optionally in a fluid carrier) including an admixed biochemicallyactive agent such as a protein can be made to form a pattern onsubstrate surface 28 according to the described technique. For example,carboxylated Dextran” can carry admixed protein, be introduced intochannels 34, and hardened to form articles 38. Where the Dextran™carries admixed biologically active agent, the article can be exposed toa medium suspected of containing a biological binding partner of thebiochemical agent, and any biochemical binding or other interactiondetected via, for example, diffraction, or via a change in couplingbetween waveguide cores as described more fully below. Where article 38defines diffraction grating, the degree of diffraction can be affectedby biological binding between the biological agent compounded withinarticle 38 and an analyte that is a biological binding partner of thecompounded agent. Determination of a change in diffraction at surface 28is indicative of the presence of analyte in the medium brought intocontact with article 38. According to another embodiment, a species suchas polymerizable or cross-linkable species can entirely coat surface 28,article 20 can be placed adjacent surface 28, a biological agent can beintroduced into channels 34 and allowed to admix with the polymerizableor cross-linkable species, and prior to or subsequent to removal ofarticle 20 species on surface 28 can be polymerized or cross-linked. Inthis manner, a surface having a pattern of biological agent compoundedtherein is produced, and can serve as a sensor for a biological bindingpartner of the biological agent via change in refraction or diffractionof light at the surface.

Where electrical conductivity is desired, an electrically-conductivepolymer can be selected, and this can have significant application inthe microelectronics industry, as would be recognized by one of ordinaryskill in the art.

The invention is intended to encompass creation of a wide variety ofstructures or patterns of species on substrate surfaces from fluidprecursors. The precursor can be any fluid that can flow into the molddefined by indentations 24 and portions 34 of substrate surface 28, andthose of ordinary skill in the art can determine, without undueexperimentation, which fluids will readily flow into such a mold basedupon dimension of the mold and viscosity of the fluid. In mostinstances, the viscosity of the fluid can be adjusted, by for examplediluting or concentrating the fluid, to achieve a level of viscositysuitable for flow into the mold at a desired rate. The polarity of thefluid can be tailored as well, with reference to the chemicalcharacteristic of the substrate surface or micromold, to facilitatefluid carrier flow.

According to one embodiment of the invention, patterned article 38 isnot a polymer or cross-linked organic species as described above, but isa non-polymerized organic species that is dissolved or dispersed in afluid carrier to form fluid precursor 36 which is introduced into moldchannels 32, whereupon the fluid carrier or solvent dissipates (e.g., isremoved via evaporation from the mold channels and/or absorption intothe substrate or applicator 20). According to yet another embodiment,patterned structure 38 is an inorganic structure, such as a salt orceramic. A salt soluble in a fluid precursor can be prepared as asolution 36 defining a fluid precursor that is introduced into moldchannels 32 and precipitated as a patterned salt structure 38 by removalof solvent via evaporation, adsorption, or other physical or chemicalchange to the surrounding environment. Inorganic salts or ceramics canbe carried as a suspension in a fluid carrier, flowed into channels 32,and precipitated or deposited. Metals, such as those commonly depositedfrom pastes in accordance with thick-film silk-screening techniques, canbe applied to defined regions of substrate surface 28 where a paste issufficiently fluid, or the paste and/or metal can be carried in a fluidas a suspension or sol in fluid precursor 36. Those of ordinary skill inthe art will recognize that a wide variety of non-electricallyconductive, electrically semi-conductive, and electrically-conductivestructures can be patterned proximate a substrate surface according tothe inventive technique. Fluid precursors of inorganic materials, suchas solutions from which materials can be precipitated, or suspensionsfrom which a fluid carrier can be removed by dissipation or evaporation,can be used to form structures, such as waveguides, from materials suchas TiO₂, TiO₂/SiO₂, ZnO, Nb₂O₅, Si₃N₄, Ta₂O₅, HfO₂, ZrO₂, or the like.U.S. Pat. Nos. 5,009,483, 5,369,722, and 5,009,483, each incorporatedherein by reference, describe many suitable precursor and waveguidematerials. Dye-doped fluid precursors can be used, and are advantageousin many situations.

Another fluid precursor can be a sol-gel precursor, and sol-geltechniques known to those of skill in the art can be used to create thesolid structures in patterns, according to the invention. Ferroelectricand electrooptic materials and sol-gel processing of a variety ofprecursors to form a variety of species is well known to those ofordinary skilled in the art and can be applied and exploited by themethod of the invention. For example, materials such as PbScTaO₃, (Pb,La)TiO₃ (PLT), LiNbO₃, KNbO₃, LiTaO₃, potassium diphosphate, potassiumtriphosphate, PbMoO₄, TeO₂, Ta₂O₅ BaTiO₃, BBO crystals,Ba_(1-x)Sr_(x)TiO₃, Pb(Zr, Ti)O₃, SrTiO₃, bismuth strontium tantalate,and the like. Other examples of sol-gel precursors that can define fluidprecursors of the invention include precursors of multicomponent glassesor ceramics containing at least one oxide, such as silicate glasses orceramics containing the oxides of aluminum, boron, phosphorus, titanium,zirconium, sodium, etc. . . Other sol-gel precursors appropriate for useare precursors of hybrid materials or organically modified ceramics,such as precursors of silicon oxycarbide or ORMOCERs. Other sol-gelprecursors appropriate for use are described by Brinker and Scherer, inSol-Gel Science; Academic Press, San Diego, 1990; Dislich,Transformation of Organometallics into Common and Exotic Materials;Nijhof, Dordrecht, 1998, volume 141; Pani, et al., J. Am. Ceram. Assoc.,1994, 77, 1242; Ramamurthi, et al., Mat. Res. Soc. Symp. Proc., 1992,271, 351; Peiying, et al., Sensors and Actuators, 1995, A49, 187; Rao,J. Electrochem. Soc., 1996, 143, 189; Li, et al., Solar Energy Materialsand Solar Cells, 1995, 39, 179, each of which is incorporated herein byreference. Where a sol-gel precursor is used, a hydrolysis andpolycondensation reaction takes place, preferably a two-step reaction.The working examples described herein use tetramethylorthosilicate asthe main constituent in glasses formed according to this reaction. Otheralkoxides react similarly. Sol-gel precursors that include mixtures ofglasses or glasses that are mixtures of compounds. These structures canbe deposited in any pattern that corresponds to an indentation patternformable in an applicator or micromold 20 and can include dimensionsthrough a wide range as described below.

The present invention, according to one aspect, involves the fabricationand use of reactive ion etch masks from sol-gel precursors. Dielectricmaterials such as aluminia, zirconia, and silica glasses and mixedglasses such as aluminosilicates can be fabricated simply, conveniently,and relatively inexpensively using the techniques of the invention. Asol-gel precursor can be formed into a pattern using any of the moldingtechniques as described herein, with reference for example to FIGS. 1,2, 8, 10, 15, 16, and 25, and can be carried out directly on a surfacethat is desirably etched via reactive ion etching. That is, an articleis provided that is desirably etched via reactive ion etching, and areactive ion etch mask is formed on a surface of the article via moldingaccording to any of the techniques described herein from a precursor ofa reactive ion etch mask. The reactive ion etch mask is formed from theprecursor using the mold defined in part by the forming article of theinvention on a first portion of the article surface, in a pattern, whileleaving a second portion of the substrate surface free of the maskmaterial. The surface of the article then is exposed to reactive ionetch conditions (known to those of ordinary skill in the art, e.g., 0₂plasma), and etching takes place at the second portion of the substratesurface. Typically, the first portion of the substrate surface will be apattern of separated lines or portions that can be isolated orinterconnected, and the second portion will be complementary to thefirst portion. The second portion is “free” of reactive ion etch maskwhen the second portion contains no reactive ion etch mask material oris covered by so little reactive ion etch mask material that exposure toreactive ion etching conditions causes reactive ion etching at thesecond portion. Formation of dielectric, or ceramic materials inaccordance with this aspect of the invention can find use not only inreactive ion etching masks but in integrated optics, non-linear opticsand other microelectronic arenas as would be understood by those ofordinary skill in the art.

According to yet another embodiment, a biologically active agent can bedissolved or suspended in a fluid carrier as a fluid precursor 36 andintroduced into channels 32 adjacent portions 34 of surface 28 and,prior or subsequent to removal of micromold 20, allowed to engage in abiochemical interaction proximate regions 34 of substrate surface 28.For example, a biochemical agent can include a biotin linker whilesubstrate surface 28 carries immobilized avidin, and biochemicalinteraction can be allowed to take place at regions 34 of substratesurface 28 in this manner, linking the biochemical agent to thesubstrate surface at regions 34. Biochemical agents can be immobilizedproximate regions 34 of the substrate surface according to othertechniques as well. For example, where substrate surface 28 exposes ahydrophobic functionality, a biological agent such as a protein can benon-covalently immobilized at regions 34 of the substrate surface. Tocontrol orientation of a protein or other biochemical agent immobilizedat a substrate surface via hydrophobic interaction, a hydrophobicchemical moiety can be coupled to the biochemical agent at a region ofthe agent remote from its active site. In this manner, the agent can behydrophobically coupled to the surface and maintain exposure, away fromthe surface, of its biochemically active region. One of ordinary skillin the art can conduct a simple test to determine whether a biochemicalagent is suitable for use with the described technique. The bindingconstant of a candidate biochemical agent for a target species can bedetermined using standard ELISA techniques. Then, the candidatebiochemical agent can be hydrophobically immobilized (or immobilized inany other manner described herein or known to those of ordinary skill inthe art, for example via a polyamino acid tag coupled to a metal ionimmobilized at the surface by a chelating agent) at a variety ofsurfaces, and then assays can be performed to determine whether theagent has retained its ability to biologically bind to the targetspecies or has been denatured and is unable to bind (this exemplary testis particularly useful in connection with biological agents that, intheir native form only, bind target species, but when denatured do notbind the target species).

Biochemical recognition can be exploited in immobilization of aparticular biochemical agent desirably patterned on substrate surface28. For example, a first agent can be immobilized (for example usinghydrophobic coupling) at regions 38 of the substrate surface, and asecond agent (which is a biological binding partner of the first agent)then can be immobilized at regions 34. The second step in which thedesired agent is immobilized at regions 34 can be carried out with orwithout micromold 20 proximate the substrate surface. Biochemicalrecognition involving partners also can be exploited to trap biologicalagents at regions 34 of the substrate surface using other biologicalagents that have been immobilized at regions 34. Biochemical recognitioninvolving partners such as antibody/antigen, antibody/hapten,enzyme/substrate, enzyme/inhibitor, enzyme/cofactor, biotin/avidin,binding protein/substrate, carrier protein/substrate,lectin/carbohydrate, receptor/hormone, receptor/effector, complementarystrands of nucleic acid, repressor/inducer, and the like can beexploited in connection with the technique. Those of ordinary skill willrecognize a variety of uses for placement of such biochemically activeagents at predetermined portions of a substrate surface in a pattern,for example as discussed below with reference to FIG. 14 and asdisclosed in co-pending, commonly-owned U.S. Pat. No. 5,512,131 ofKumar, et al. and International Patent Application Publication No. WO96/29629, both incorporated herein by reference.

According to embodiments in which the biochemical activity of abiologically active agent can be detrimentally affected by environmentalfactors, a fluid carrier of the biologically active agent should beselected so as not to detrimentally affect the biochemical activity ofthe agent. For example, if a protein is to be patterned on the surfaceand used in an interaction that cannot take place (or takes place at anunacceptably low level) when the protein is denatured, a fluid carriershould be selected that does not denature the protein or otherwisedetrimentally affect the biological binding interaction of the proteinthat is to be exploited. Additionally, a micromold 20 should be selectedand/or fabricated in a manner such that the surfaces of indentations 24that can come into contact with a biologically active agent will notdetrimentally affect the performance of the agent. For example, ifmicromold 20 is fabricated from a material that could denature aprotein, then if used with the protein the interior surfaces ofindentations 24 can be chemically altered, for example via grafting withpolyethylene glycol, to render the surfaces non-destructive of theagent.

According to yet another embodiment, fluid precursor 36 carries asuspended or dissolved chemically active agent that is an activatingagent as described in a co-pending, commonly owned U.S. application Ser.No. 08/616,692 of Hidber, et al. entitled “Microcontact Printing ofCatalytic Colloids”, referenced above. When a fluid carrier is used inthis and other embodiments, it can form part of a species or articleimmobilized proximate the substrate surface or can dissipate, forexample via evaporation or adsorption into the applicator or substratesurface, leaving the species carried in the fluid carrier immobilized atthe surface.

A non-limiting list of chemically active agents that can be patterned ona surface in accordance with the invention includes agents as describedby Lando (U.S. Pat. Nos. 3,873,359; 3,873,360; and 3,900,614) which canrender a substrate surface amenable to metal plating, catalyticactivating agents such as finely distributed metal particles andclusters such as conventional metal powders, substrate-fixed metalclusters or multimetallic clusters that are well known as valuableheterogeneous and homogeneous catalysts in organic chemistry, inorganicchemistry, and electrochemistry, etc. With reference to the applicationof Hidber, et al., such agents can include those capable of beingcarried by an applicator, transferred from the applicator to a surfacein a form in which it can effect a chemical reaction (such as a metaldeposition reaction), and immobilized at the surface with a degree ofadhesion and for a period of time sufficient to participate in thedesired chemical reaction. As such, one class of activating agentsprovided in accordance with the invention are distinguished from priorart agents applied with an applicator such as a stamp, for example asdisclosed by Lando (U.S. Pat. Nos. 3,873,359, 3,873,360, and 3,900,614),in that the activating agent of the present invention is in a formsuitable for effecting reaction such as metal plating or catalyticaction when transferred to the surface. According to preferredembodiments, further chemical reaction at the surface to convert aprecursor to a suitable agent, as necessitated in the referenced priorart methods, is not required. Metal deposition reactions contemplatedinclude electrochemical deposition and electroless deposition, generallyinvolving reduction of a, metal cation to create the metal, facilitatedin part by the lowering of the electrochemical potential involved in thedeposition.

Activating agents that are finely distributed metal particles andclusters, such as conventional metal powders, including substrate-fixedmetal clusters or multimetallic clusters are suitable for use asactivating agents in accordance with the invention, and are well knownas valuable heterogeneous and homogeneous catalysts in organic,inorganic, and electrochemistry. Exemplary activating agents include oneor more metals of periodic table groups Ib, IIb, III, IV, V, VI, VIIb,VIII, lanthanides, and actinides, preferably copper and any metal morenoble than copper, in particular Pd, Au, Ag, Pt, and Cu. Hydrogenationcatalysts for example those effective in hydrogenating olefins oraromatics, as in the partial hydrogenation of benzene to formcyclohexene, with a substrate-fixed ruthenium activating agent orbimetallic activating agent (e.g. Ru/Sn) are contemplated. Zirconium andtitanium catalysts, among others, are suitable for use in the inventionthat catalyze polymerization, such as polymerization of olefins such asethylene, and these are intended to form part of the invention. Otherexamples of catalytic activating agents include those used in Heckreactions, e.g. in the Pd-catalyzed reaction of bromobenzene and styreneto form stilbene. Activating agents that are heterogeneous catalysts arealso useful as electrocatalysts in fuel cells (in particularsubstrate-fixed Pt and Pt/Ru clusters). Activating agents preparedaccording to the invention can be homogeneous catalysts, such as thoseused in two phase systems (for instance H₂O/toluene), such as e.g.betaine-stabilized Pd clusters soluble in H₂O. Activating agents thatare embedded in polymers can be used to prepare materials forelectronic, optical and magnetic applications. Suitable embeddingpolymers include organic polymers, such as poly-p-phenylene-vinylene,polymethyl methacrylate, polysilanes, and polystyrene, or inorganicpolymers, such as zeolites, silicates, and metal oxides. The well-knownsol-gel process can be used to incorporate metal clusters in amorphousmetal oxide materials (e.g. SiO₂) as activating agents.

Soluble metal clusters that are activating agents can also besurface-deposited to prepare novel materials for applications in opticsand electronics, e.g. Pd on HOPG (highly oriented pyrolytic graphite).

Particulate activating agents having particle sizes on the order ofnanometers are preferred, for example particulate matter having particlesize of less than about 100 nm, preferably less than about 50 nm, morepreferably less than about 25 nm, and most preferably from about 2 toabout 20 nm. The size of the particles is not critical except to theextent that where excellent edge resolution of a structure deposited ina reaction involving the particle is desired, the upper limit in size ofthe particle is reduced.

Especially preferred as activating agents in accordance with theinvention are colloidal activating agents. As used herein, colloidalactivating agent is meant to define particulate matter capable of beinginvolved in a desired chemical reaction, such as a catalytic reactionand including plating of metal at surfaces, that is carried orsurrounded by molecules that prevent agglomeration of the individualparticles and that render the particulate soluble in, or at least ableto be carried in, an organic or aqueous liquid. Suitable colloid-formingspecies and colloids are described in European patent publication no.672765 by Reetz et al., published Sep. 20, 1995, and incorporated hereinby reference. According to one embodiment the activating agent comprisesone or more metals of groups Ib, IIb, III, IV, V, VI, VIIb, VIII,lanthanides, and/or actinides of the periodic table prepared by cathodicreduction in the presence of a stabilizer. One method of preparation ofsuch colloids is reduction, optionally with a supporting electrolyte, inorganic solvents or in solvent mixtures of organic solvents and/or waterwithin a temperature range of between about −78° C. and about 120° C. toform metal colloidal solutions or redispersible metal colloid powders,optionally in the presence of inert substrates and/or soluble metalsalts of the respective metals. These colloids are soluble orredispersible in a suitable fluid that facilitates their application toan applicator such as a stamp. The following articles, incorporatedherein by reference, describe as well exemplary activating agentssuitable for use in connection with the invention. Vargo, et al.,“Adhesive Electroless Metallization of Fluoropolymeric Substrates”Science, 262, 1711-1712 (Dec. 10, 1993); Bönnemann, et al., “Preparationand Catalytic Properties of NR₄ ⁺ Stabilized Palladium Colloids”,Applied Organometallic Chemistry 8, 361-378 (1994); Reetz, et al.,“Size-Selective Synthesis of Nanostructured Transition Metal Clusters”J. Am. Chem. Soc. 116, 7401-7402 (1994); Reetz, et al., “Visualizationof Surfactants on Nanostructured Palladium Clusters by a Combination ofSTM and High-Resolution TEM”, Science, 267, 367-369 (Jan. 20, 1995); andMeldrum, et al., “Formation of Thin Films of Platinum, Palladium, andMixed Platinum Palladium Nonocrystallites by the Langmuir MonolayerTechnique” Chem. Mater., 7, 111-116 (1995).

Electrochemical methods are described in EP 672765, referenced above,for synthesis of soluble metal colloids by operating in an inertorganic, aprotic solvent, with surface-active colloid stabilizers beingadded as the supporting electrolyte which will both prevent plating ofthe metal and protect, or stabilize, small metal nuclei in the clusterstage. A metal sheet serves as the anode to be dissolved and a metal orglassy carbon electrode serves as the cathode. After dissolution at theanode, the released metal salts are reduced again at the cathode, withtetraalkylammonium salts serving as stabilizers. Standard organicsolvents can be employed.

Suitable exemplary stabilizers, or carriers, for the colloids, and atthe same time as the supporting electrolyte, are quaternary ammonium orphosphonium salts R¹R²R³R⁴N⁺X⁻ and R¹R²R³R⁴P^(+X) ⁻, respectively. Awide variety of combinations of R¹, R², R³ and R⁴ are possible. Examplesinclude the symmetrical tetraalkylammonium salts withR¹=R²=R³=R⁴=n-butyl or n-octyl, mixed tetraalkylammonium salts withR¹=R²=R³=methyl and R⁴=cetyl, or chiral tetraalkylammonium salts havingfour different residues.

Aryltrialkylammonium salts may also be used. Suitable counter ionsinclude various anions, e.g. halogenides (Cl⁻, Br⁻, I⁻),hexafluorophosphate (PF₆ ⁻), carboxylates R′CO₂ ⁻ (R′=alkyl, aryl), orsulfonates R″SO₃ ⁻ (R″=alkyl, aryl). A similar variety of phosphoniumsalts may be used, including tetraarylphosphonium salts, such astetraphenylphosphonium bromide. Preferably, tetrabutylammonium chloride,bromide or hexafluorophosphate, tetraoctylammonium bromide, ortributylhexadecylphosphonium bromide can be employed. As metals, any ofthose listed above, in particular transition metals such as Fe, Co, Ni,Pd, Pt, Ir, Rh, Cu, Ag, or Au, are suitable. Suitable solvents areaprotic organic solvents, such as tetrahydrofuran (THF), toluene,acetonitrile (ACN), or mixtures thereof. The temperature in theelectrolytic cell may be in the range between −78° C. and +120° C.,preferably 15-30° C. or room temperature.

A preferred activating agent is a colloidal catalyst that promotesdeposition, for example electroless deposition, of a metal at region 34of substrate surface 28 to which the colloidal catalyst is applied. Forexample, where fluid precursor 36 includes a suspension of a colloidalpalladium catalyst, the fluid can be evaporated or adsorbed as describedabove, resulting in deposition of catalyst at regions 34 of substratesurface 28. Subsequently, an electroless copper plating bath can beintroduced into channels 32 and deposition of copper allowed to takeplace at regions 34 of surface 28. Alternatively, micromold 20 can beremoved from surface 28 and the entire surface 28 exposed to anelectroless copper plating bath. Copper will plate only at those regions34 of substrate surface 28 to which colloidal palladium catalyst hadbeen applied. Electrochemical metal plating can be carried out as well.The chemically active agent of the invention can be any agent that canfind use in chemical reaction, attraction, or other interactionproximate a substrate surface. Those of ordinary skill in the art willrecognize a variety of agents that can be used in accordance with theinvention, including, but not limited to solutions or suspensions of avery small species such as catalytic colloids, monomers, dissolved orsuspended salts or ceramics or their precursors or other species.

According to yet another embodiment of the invention a suspension ofparticulate species in a fluid carrier 36 can be introduced intochannels 32, followed by removal of the fluid carrier via dissipation,as discussed. The particulate species can be organic, inorganic, orpolymeric material as described above, for example finely-groundpolymeric, ceramic, or crystalline material, or can be in the form ofmicrospheres. The application of microspheres in a predetermined patternto a substrate surface can serve a variety of purposes that will beapparent to those of ordinary skill in the art upon reading the presentdisclosure, in light of the state of the art as set forth in severalpublications. An article by Lenzmann, et al., entitled “Thin-FilmMicropatterning Using Polymer Microspheres”, Chem. Mater., 6, 156-159(1994), incorporated herein by reference, describes formation ofdensely-packed monolayers of monodisperse polystyrene microspheresdeposited on a glass substrate. The spheres serve as a mask for zincsulfide deposition on the substrate as a thin film by thermalevaporation in vacuum. The mask (microspheres) are removed from thesubstrate surface after evaporative deposition leaving behind a surfacewith zinc sulfide features located in the interstitial spaces of thedensely-packed spheres. For 2-micron diameter spheres, the latticespacing of the resulting pattern is approximately 900 nanometers withindividual trigonal pyramidal peaks. According to the present invention,a particular concentration of polymeric microspheres in a fluid carriercan be selected without undue experimentation that, when introduced intochannels 32, followed by evaporation of the fluid carrier, would resultin a monolayer of microspheres selectively patterned at regions 34 ofsubstrate surface 28. Removal of micromold 20, followed by chemicalvapor deposition, results in a well-ordered pattern of isolated,nano-scale regions of deposited material within the confines of region34 of substrate surface 28.

An article by Dushkin, et al. entitled “Colored Multilayers FromTransparent Submicrometer Spheres”, Langmuir, 9, 3695-3701 (1993),incorporated herein by reference, discusses optical phenomena associatedwith polymeric beads at surfaces. Ordered multilayers are formed byevaporating the water carrier from polystyrene latex suspensions ofdiameter smaller than the wavelength of visible light. The spheresexhibit color when illuminated with polychromatic light. Accordingly,arrangement of a pattern of microspheres at regions 34 of substratesurface 28 in accordance with the invention can result in variousradiative and colorimetric phenomena. An article by Hayashi, et al.entitled “Imaging by Polystyrene Latex Particles”, Journal of Colloidand Interface Science, 144, 2, 538-547 (July, 1991), incorporated hereinby reference, describes microarrays of identical images produced bypolydispersed polystyrene particles at a surface. Microparticles andmicrobeads, especially polymeric particles and beads such as latex orpolystyrene beads, find use in the field of biochemistry as solidsupports for biochemical interaction. For example, a chemically orbiochemically active agent can be coupled to a microbead ormicroparticle and optionally used in turn to immobilize a second agentthat reacts with the immobilized agent, thereby immobilizing the secondagent at a region at which the microbead is immobilized. That is,microbeads carrying a particular agent can be immobilized at a surfacein a pattern using techniques of the invention and the patterned,immobilized beads can serve as locations for chemical reaction orbiochemical interaction on the micro scale, for example asmicroreactors. Those of ordinary skill will recognize a variety of usesfor patterned microparticles or microbeads carrying chemical orbiochemical agents such as, for example, biochemical assays.

The pattern of parallel indentations 24 formed in surface 22 ofmicromold or applicator 20 is for illustrative purposes only. Anypattern, for example a pattern defined by a single indentation or manyindentations, one or more of the indentations defining a non-linearpathway of uniform or non-uniform depth is intended to fall within thescope of the invention. Various patterns are illustrated in subsequentfigures. The indentation pattern can be of a variety of dimensions and,according to one aspect of the invention, includes a region having alateral dimension of less than 1 millimeter. “Lateral dimension” ismeant to define a dimension parallel to application surface 22.According to preferred embodiments, the indentation pattern includes aportion having a lateral dimension of less than about 500 microns orless than about 100 microns, in one set of embodiments more preferablyless than about 50, 20, or 10 microns, and more preferably still lessthan about 5 microns. According to a particularly preferred embodiment,an indentation pattern having a portion including a lateral dimension onthe order of 1 micron is provided. The dimension of the indentations canbe altered, as described in international patent publication number WO96/29629, published Jun. 26, 1996 of Whitesides, et al., entitled“Microcontact Printing on Surfaces and Derivative Articles”,incorporated herein by reference, by deforming article 20. Wherewaveguides are fabricated in accordance with the invention, it is anadvantage that, for example, branched sections and/or evanescentcoupling sections, as shown in FIGS. 17 and 18 can be included in thepattern. Those of ordinary skill in the art can select suitabledimensions, depending upon the frequency of electromagnetic radiationbeing guided. Typically, the waveguide will have a width on the order ofmicrons. The technique can be carried out where micromold 20 includes anindentation pattern where the indentations have depths and widths on theorder of 100 microns to less than 1 micron, controllably.

Where micromold 20 is placed adjacent a substrate surface and a fluidprecursor fills channels 32, article or articles 38 resulting from thetechnique can have lateral dimensional features that correspond to thelateral dimensional features of indentations 32 of the micromold.

According to another embodiment, the fluid precursor need not completelyfill channels 32, and this is preferred according to embodiments inwhich the lateral dimension of article 38 formed from the fluidprecursor is to be minimized. According to this embodiment, fluidprecursor 36 is introduced into channels 32 in an amount small enoughthat the fluid precursor wets only the corners of the channels. When afluid precursor, substrate, and micromold are selected such that thefluid precursor will wet the micromold efficiently via capillary action,when a small amount of fluid precursor is supplied to the mold channelor channels, the precursor will selectively wet portions of the channelshaving an interior angle relatively low relative to the rest of thechannel (such as corners 40 defined by the abutment of contact surface26 against substrate surface 28 at the edge of region 34 of thesubstrate surface). When the fluid precursor wets the cornersselectively and the fluid is hardened, evaporated, or adsorbed, aresulting structure can define a pattern having a dimension smaller thanthat of the lateral dimension of indentation 24. According to thisembodiment the lateral dimension of structure 38, at its narrowest, isnarrower than the narrowest lateral dimension of channel 24 of themicromold, and can have a height significantly less than the height ofthe channel. The lateral dimension of article 38 according to thisembodiment can be on the order of less than or equal to about 100microns or 50 microns, or preferably less than about 20 or 10 microns,more preferably less than about 5 microns or 1 micron, and according toa particularly preferred embodiment less than approximately 0.2 micron.According to this aspect, any of the species described herein that canbe patterned proximate a substrate surface can be patterned so as tohave lateral dimensions as described above. This aspect of the inventionis illustrated in FIG. 6c, and discussed below.

In an alternate technique, any of the species described herein that canbe used to form patterned articles and the like on a substrate surface(such as fluid precursor 36) can be made to coat substrate surface 28,and then article 20 can be pressed against substrate surface 28 todisplace precursor 36 at regions in register with contact surface 26.Precursor 36 will be formed in channels 32 as illustrated in FIG. 1, andprocedures described above carried out.

Any suitable material can define substrate 30 of the invention.Substrate surface 28 can be of the same material as the bulk material ofsubstrate 30, or a different material. Substrates exposing a variety offunctional surfaces such as hydrophobic, hydrophilic, and biologicallycompatible or non-compatible surfaces are known, and are suitable foruse with the invention. Substrates that are somewhat fluid are known aswell, and are acceptable for use in the invention to the extent that auseful pattern can be formed thereupon. Article 20 similarly can beformed of essentially any material. For example, ceramic, polymeric,elastomeric, and other materials can be used. According to a preferredembodiment, substrate surface 28 and/or contact surface 26 of article 20is an elastomer or other conformable material. Preferably, contactsurface 26 and more preferably, for ease of fabrication, the entirearticle 20, is formed of an elastomer. When an elastomer definessubstrate surface 28 or contact surface 26, or preferably micromold 20,an optimal seal is created between contact surface 26 and portions ofsubstrate surface 28 adjacent and contiguous with portions 34 that withindentations 24 define channels 32. This results in optimal confinementof fluid precursor 36 to channels 32. According to the inventionpressure can be applied to micromold 20 against substrate 30 duringmicromolding, but according to embodiments in which an elastomer is usedas described, pressure need not be applied as the elastomer conformswell to the surface against which it mates thus sealing channels 32. Themicromold 20 can be fabricated of an elastomer in a manner analogous tothe fabrication of a stamp from an elastomer as described in co-pending,commonly-owned U.S. Pat. No. 5,512,131, issued Apr. 30, 1996 by Kumar,et al, entitled “Formation of Microstamped Patterns on Surfaces andDerivative Articles”, and as described in International PatentPublication No. WO 96/29629 of Whitesides, et al., entitled“Microcontact Printing on Surfaces and Derivative Articles”, publishedJun. 26, 1996, both of which are incorporated herein by reference,

FIG. 2 illustrates another embodiment of the invention in which, ratherthan applying article 20 to substrate surface 28 followed byintroduction of fluid precursor 36 into channels 32 so defined, article20 is used as an applicator to transfer a chemically or biochemicallyactive agent (optionally in a fluid carrier), fluid precursor of anarticle such as microparticles or microbeads in suspension, catalyticcolloid, prepolymer fluid, or the like to substrate surface 28.Described below with reference to FIG. 15 is a set of transfer moldingtechniques particularly preferred in the fabrication of waveguides andother articles where the final shape of the formed article isessentially identical to the shape of the interior of the mold. In FIG.2 and subsequent figures, components common to the various figures aregiven common numerical designation. In FIG. 2, fluid precursor 36 isfirst applied to indentations 24 of micromold 20, and then applicationsurface 22 is brought into proximity of substrate surface 28 to allowfluid precursor 36 to be transferred to substrate surface 28. The fluidprecursor can be applied to the indentations by bringing theindentations into contact with the fluid precursor and allowingcapillary action to cause the indentations to be filled, or theprecursor can be applied via micropipetting or the like to theindentations. In this way, separate fluid species can be applied toseparate indentations if desired. In can be advantageous, with thesetechniques, to select a material exposed by the contoured applicationsurface and the fluid species applied thereto such that the fluidspecies rapidly is positioned within the indentations, rather thanspreading over the entire surface. Those of skill in the art can carryout such selection, using contact angle measurements or the like.

Where fluid precursor 36 protrudes from indentations 24 prior totransfer, application surface 22 need not contact substrate surface 28for transfer to take place. Typically, however, application surface 22will be brought into contact with substrate surface 28 to transfer apattern of the fluid precursor 38 to regions proximate the substratesurface in a pattern corresponding to the indentation pattern 24. Asillustrated, some fluid precursor remains in indentations 24, and thefluid precursor transferred to substrate surface 28 has been convertedinto hardened article 38. However, according to several embodimentsdiscussed above, the fluid precursor will not result in a hardenedarticle, but will serve to transfer a biochemical agent or chemicalagent to a surface. According to the embodiment illustrated in FIG. 2,the chemical or biochemical agent, prepolymer, fluid carrier containinga suspension of particulate matter, microbeads, or the like serves totransfer essentially instantaneously the desired species to the surface.As with all embodiments of the invention, the pattern of species sotransferred can include a single indentation that is of any shapeincluding a non-linear or linear pathway, a plurality of linearindentations as illustrated in FIG. 2, or a plurality of indentations ofany shape, one or more indentations having dimensions as describedabove. Where a plurality of indentations are formed in applicationsurface 22, each indentation can be made to carry a different chemicalor biological agent or precursor. According to that embodiment, whenapplication surface 22 of the micromold is brought into contact withsubstrate surface 28, distinct first and second species such as distinctfirst and second chemically or biochemically active agents, precursors,particulate species, or the like can be transferred essentiallyinstantaneously to distinct first and second regions 42 and 44 proximatethe substrate surface, in a pattern corresponding to the indentationpattern, and separated from each other by intervening region 46 of thesubstrate surface that remains free of the agent or precursor.

FIGS. 3a-d are photocopies of SEM images of polymeric structures formedon substrates according to the method described above and illustrated inFIG. 1, in which a fluid polymeric precursor was allowed to fillchannels formed by indentations in micromold 20 and regions of thesubstrate. FIG. 3a shows polyurethane articles 48 formed on Si/SiO₂substrate 50 by capillary filling of a micromold having a surface withindentations placed adjacent substrate 50. The indentations correspondto the pattern of articles 48. A liquid polyurethane prepolymer wasplaced adjacent openings of channels formed between the micromold andthe substrate surface and filled the channels via capillary action. Themicromold was made of polydimethylsiloxane (PDMS). FIG. 3b is a top viewof a polyurethane article 52 having a complex, interconnected patternformed on Si/SiO₂ substrate 50. A PDMS micromold having an indentationpattern corresponding to the pattern of article 52 was used, and aliquid polyurethane prepolymer was allowed to fill the mold channels viacapillary action. FIG. 3c shows a quasi three-dimensional array ofmicrostructures interconnected through channels. Again, a polyurethaneliquid prepolymer was allowed to fill channels formed by a micromoldhaving an indentation pattern corresponding to the pattern ofpolyurethane article 54. Polyurethane article 54 is formed on a Si/SiO₂substrate 50. FIG. 3d shows a free-standing patterned polyurethanearticle 52 formed by removal of the article from the substrate (FIG.3b).

FIGS. 4a-h illustrate structures formed on substrates using themicromolding technique illustrated in FIG. 1 in which liquid precursor36 is a precursor of inorganic materials. Photocopies of SEM images areshown. In FIG. 4a, KH₂PO₄ structures precipitated from aqueous solutionon Si/SiO₂ are shown. FIG. 4b shows KH₂PO₄ structures as well,crystallized more rapidly. FIG. 4c shows Cu(NO₃)₂ on the same substratecrystallized from aqueous solution. FIG. 4d shows structures formed ofthe same material on the same substrate, but crystallized from a muchmore dilute solution. FIG. 4d illustrates the derivatization in apattern that is formed within the boundaries of a region of thesubstrate surface corresponding to the indentation pattern of themicromold, but that does not fill that region. A series of isolatedregions of product on the order of 4 microns in lateral dimension areshown. FIG. 4e shows CUSO₄ structure on glass. FIG. 4f shows K₃Fe(CN)₆structures on Si/SiO₂. FIG. 4g shows a fractured view of amaranth onglass. The structures are approximately 0.4 micron in height. FIG. 4h isa section of FIG. 4g at higher magnification.

Ceramic structures formed in accordance with the invention can find use,for example, as mechanical ceramics such as abrasion tools. Currentmethodologies involve, typically, chemical vapor deposition to formceramic patterns having small dimensions for such uses.

FIG. 5 is a photocopy of an electron micrograph showing a packed,ordered array of polystyrene microspheres 70 on a Si/SiO₂ substrate 72.The ordered array of microspheres was formed by allowing a latexsolution containing polystyrene microspheres to fill, via capillaryaction, channels formed between a micromold and the substrate surface ina pattern corresponding to the pattern of microbeads shown. The PDMSmicromold was removed following crystallization of the microspheres viadissipation of the fluid carrier.

FIGS. 6a-c are photocopies of SEM images of copper structures formed viaelectroless deposition on Si/SiO₂ substrates. For the structure in FIG.6a, a gold surface was provided. A PDMS micromold having an indentationpattern corresponding to the pattern of copper structures illustratedwas placed adjacent the gold substrate (as illustrated schematically inFIG. 1) and the channels 32 were filled with a plating bath forelectroless deposition of copper, defining a fluid precursor of copperaccording to one aspect, and a chemically active agent according toanother aspect. The copper electroless plating solution was allowed toremain in contact with the surface for a period of time sufficient toplate copper structures 74 in a pattern corresponding to the indentationpattern of the micromold, while portions of gold surface 76corresponding to contact surface 26 of the micromold remained free ofcopper deposition. For the structure illustrated in FIGS. 6b-c, a PDMSmicromold having an indentation pattern corresponding to the pattern ofcopper structures illustrated was placed adjacent the substrate and thechannels 32 were filled with a precursor solution 36 containingcatalytic colloids. The solvent in which the catalytic colloidsdissipated, resulting in formation of the catalytic colloids as achemically active agent formed on regions of the substrate surfacecorresponding to the indentation pattern of the micromold. The micromoldwas removed, and the surface exposed to an electroless copper platingbath. Specifically, in FIG. 6b, copper structures 78 were formed on aSi/SiO₂ substrate 80 coated with a self-assembled monolayer of siloxaneon the Si/SiO₂ substrate. CH₃CH₂O)₃Si(CH₂)₃NH₂ defined theself-assembled monolayer. A micromold having an indentation patterncorresponding to the ultimate copper pattern 78 was placed on theself-assembled monolayer-derivatized silicon substrate. A DMF solutioncontaining palladium colloids as a fluid precursor 36 was allowed tofill the channels. Dissipation of DMF resulted in the chemically activeagent (specifically, palladium colloid) forming structures in a patterncorresponding to pattern 78. The substrate was exposed to an electrolesscopper plating bath to plate copper at patterned region 78. FIG. 6cillustrates an aspect of the invention in which articles of very smalllateral dimension can be formed by allowing a small volume of fluidprecursor 36 to enter channels 32 defined by the micromold indentationsand the substrate surface. The substrate was prepared as described inconnection with FIG. 6b. A region 82 of the substrate surfacecorresponds to the indentation pattern of the micromold. The fluidprecursor 36 wetted only the corners defined between the substratesurface 84 and the micromold channels thus, when the fluid carrierdissipated, the catalytic colloid was solidified only in those portionsof the indentation pattern that were wetted, namely, the corners. Whenthe surface was exposed to an electroless copper plating bath, copperwas plated at the regions 86 to which the catalytic colloid had beendeposited. A copper pattern of very small lateral dimension resulted.

FIGS. 7a-c illustrate the application of a patterned structure to asurface from a fluid precursor using micromolding as illustrated in FIG.1, followed by use of the structure as a resist in a chemical etch. Apolymeric structure 88 (polyurethane) was formed from a fluid prepolymerin a pattern corresponding to an indentation pattern on a 200 nm,thermally grown oxide layer 90 of a silicon substrate 92 (FIG. 7a).Following exposure of the substrate to a solution (aqueous HF/NH₄F forabout 2 minutes) that etches silicon dioxide, but to which the polymericstructure 88 was resistant, the silicon dioxide layer was removed atregions of the substrate intervening the regions covered by thepatterned structure 88, that is, regions that had been contacted bycontact surface 26 of the micromold (FIG. 7b). Subsequently, thesubstrate surface was exposed to a solution (400 ml H₂O, 92 g KOH, 132ml 2-propanol for about 15 minutes at 65° C.) that etches silicon, butto which silicon dioxide is resistant. FIG. 7c shows resultant channels94 anisotropically etched in the silicon substrate between patternedregions of silicon dioxide 90 that correspond to the pattern ofpolymeric structure 88 formed on the substrate surface via themicromolding technique.

FIG. 8 illustrates schematically a technique for forming a mask, for usein lithography or the like, via the micromolding technique of theinvention. A micromold 96 having a molding surface 98 including aplurality of indentations 100 in a grid-like pattern is applied to asurface 102 of a substrate 104. A fluid polymeric precursor 106 isplaced adjacent openings of channels formed between the substratesurface and the indentations of the micromold, and allowed to flow, viacapillary action, into the channels. Where a PDMS micromold was used,the polymeric precursor could be placed so as to cover all channelopenings, and flowed into and made to fill the channels completely. Gasescaped presumably via diffusion through the micromold. Once thepolymeric precursor was hardened, via thermal or photolyticpolymerization or the like, the micromold was removed. The substratethen was separated from the resultant patterned article 108. Thepatterned article had a “frame” 110 completely surrounding it whichcould be used for ease of manipulation. The frame could be removed aswell, to form the article 108 in a pattern corresponding to theindentation pattern of the micromold free of the frame.

The article 108 could be used as a mask, for example as illustrated inFIGS. 9a-d, which are photocopies of SEM images. FIG. 9a shows apolyurethane mask 108 formed as illustrated in FIG. 8, and followingformation placed on a Si/SiO₂ substrate 112. FIG. 9b shows the mask 108on the substrate 112 following evaporation of gold onto the substrate. Aportion of the mask was removed and mask 114 and portions 112 of thesubstrate not covered by the mask are shown covered with gold. Portions116 of the substrate that had been covered by mask 108 remain free ofgold. FIG. 9c shows a surface having a pattern of isolated regions 118of gold on a silicon substrate (regions 120 of the silicon substrate notcovered by regions 118 of gold can be seen) formed as follows. A maskfabricated as described above was placed (with reference to FIG. 8) on asilicon substrate carrying a thin film of gold. A self-assembledmonolayer-forming species (hexadecanethiol) was exposed to the surfaceand formed a self-assembled monolayer selectively at regions 118 notcovered by the mask. The mask then was removed from regions 120, and thesurface exposed to a solution that etched gold, but to which theself-assembled monolayer was resistant. The self-assembled monolayerthen was removed, resulting in the regions 118 of gold that had beenprotected by the secondary, self-assembled monolayer resist, isolated byregions 120 of the silicon substrate. FIG. 9d shows a surfacederivatized as described with respect to FIG. 9c, but the self-assembledmonolayer was transferred to regions 118 of the surface by placing aflat PDMS article that had been coated with a self-assembledmonolayer-forming species on top of the mask 108 for one minute.

Mask 108 also could be applied to nonplanar surfaces followed byplating, etching, or the like. It can be advantageous, when transferringmask 108 to a surface having very fine features, such as a surfaceetched as illustrated in FIG. 7c, to transfer mask 108 to such a surfaceby floating it in a fluid that is supported by the surface and allowingthe fluid to dissipate or run off.

As described in international patent publication number WO 96/29629,published Jun. 26, 1996 of Whitesides, et al., referenced above, etchingor plating at a surface can be made to take place selectively atpredetermined regions, and this technique can be exploited using thetechniques of the present invention as described herein. Additionally,where a self-assembled monolayer is patterned, a “protecting species”that is resistant to (for example, incompatible with) a chemical etchcan be placed on top of a self-assembled monolayer, followed by etchingat regions not covered by the self-assembled monolayer, as described inpublication no. WO 96/29629. Of course, a self-assembled monolayer canbe incompatible with an etch and etching can take place without the useof a protecting species. The protecting species, according to thisembodiment, is compatible with the self-assembled monolayer. Accordingto another embodiment, a protecting species is less compatible with theself-assembled monolayer than with the substrate surface that is exposedat regions intervening the self-assembled monolayer. According to thisembodiment, after patterning of a self-assembled monolayer a protectingspecies is exposed to the surface and when the surface is exposed to anetchant, the surface is etched at regions that had been covered by theself-assembled monolayer.

FIGS. 10a-c illustrate formation of a mask 122 on a thin layer 124 ofchromium on a glass substrate 126 using the micromolding procedure asillustrated in FIG. 1, followed by etching of chromium at regions 128not covered by the mask. In FIG. 10a, the molding technique describedabove is used to form a pattern of polyurethane article 122 on chromium124 leaving region 128 of chromium uncovered. The surface was exposed toan etchant (400 ml H₂O, 24 ml of 63% HNO₃, 62 g NH₄NO₃.Ce(NO₃)₃ forabout 1 minute) that removes chromium but to which the polymeric article122 is resistant. The result was a glass substrate 126 having thereon apatterned mask 130 defined by chromium protected from the etch by mask122 in the pattern corresponding to mask 122 (and the patterncorresponding to the indentation pattern of the micromold). FIG. 10b isan optical micrograph of the chrome mask 130, top view. The chrome mask130 was removed from the substrate 126 and placed on a photoresistarticle. FIG. 10c is a photocopy of an SEM image of a pattern that wasgenerated in the photoresist film at regions 132 not protected by themask. Raised portions 134, in a pattern corresponding to the pattern ofthe chromium mask, and corresponding to the original indentation patternof the micromold from which the mask 122 was formed, were not ablated inthe photolithography process.

According to another embodiment a substrate surface such as a siliconwafer can be spin-coated with photoresist. A micromold can be placedadjacent to a photoresist and channels defined thereby filled with asolvent that dissolves photoresist but not the micromold. A pattern ofthe silicon wafer not covered by photoresist, the pattern correspondingto the indentation pattern of the micromold, is thereby produced.Further processing familiar to those of ordinary skill in the art can becarried out.

FIG. 11 illustrates schematically an applicator 136 that can be used forapplying any of the above-described chemically or biochemically activeagents, polymeric precursors, fluid precursors of solid structures,fluid carriers of particulate matter, and the like to a substratesurface. Applicator 36 includes a plurality of isolated indentations 138separated from each other by intervening regions of a surface 140 inwhich the indentations are formed. As illustrated, two of theindentations contain fluid carrier 142 and fluid carrier 144,respectively. The fluid carriers 142 and 144 can be the same ordifferent. A substrate 146 is shown that, for purposes of illustration,includes a self-assembled monolayer 148 formed thereon which can serveas an adhesion promoter. Fluid carriers 142 and 144 are transferred toisolated regions proximate the surface of substrate 146, in particular,regions of the exposed self-assembled monolayer 148: on the surface ofsubstrate 146. The transfer typically takes place by bringing thesurface 140 of the applicator into contact with the self-assembledmonolayer 148 but, if the fluid carriers 142 and 144 protrude from theindentations, the surface 140 need only be placed in close proximity tothe self-assembled monolayer 148.

Fluid carriers 142 and 144 can be any of the species described aboveand, according to a particularly useful embodiment, carry or define achemically or biochemically active agent that can be used in asubsequent assay or the like. For example, a self-assembled monolayer148 can be a monolayer of a species X-R-Ch as described in U.S. Pat. No.5,620,850, issued Apr. 15, 1997 to Bamdad, et al., entitled “MolecularRecognition at Surfaces Derivatized with Self-Assembled Monolayers”,incorporated herein by reference. These species have the general formulaas above where X represents a functional group that adheres to a goldsurface, R represents a spacer moiety that promotes formation of aself-assembled monolayer of a plurality of the molecules, and Chrepresents a bidentate, tridentate, or quadradentate chelating agentthat coordinates a metal ion. The chelating agent includes a chelatingmoiety and a non-chelating linker moiety, such that it can be covalentlylinked via its linker moiety to the spacer moiety while allowing thechelating moiety to coordinate a metal ion. According to a preferredaspect of the invention a metal ion is coordinated to the chelatingagent, and a binding partner of a target molecule is coordinated to themetal ion. This arrangement is facilitated by selecting the chelatingagent in conjunction with the metal ion such that the chelating agentcoordinates the metal ion without completely filling the ion'scoordination sites, allowing the binding partner to coordinate the metalion via coordination sites not filled by the chelating agent. Anon-limiting exemplary list of suitable chelating agents includesnitrilotriacetic acid,2,2′-bis(salicylideneamino)-6,6′-demethyldiphenyl, and1,8-bis(a-pyridyl)-3,6-dithiaoctane. The binding partner can be abiological species that includes a polyamino acid tag, such as a tagmade up of at least two histidine residues, that coordinates the metalion. In this context the term “adhere” means to chemisorb in the mannerin which, for example, alkyl thiols chemisorb to gold.

In this case the fluid carriers 142 and 144 can be carriers of a nickelion, resulting in a surface suitable for capture of a biological bindingpartner carrying a polyamino acid tag selectively at regions to whichcarriers 142 and 144 had been applied. According to this embodiment,immediately following application of carriers 142 and 144 to thesubstrate surface, it can be advantageous to expose the surface ofsubstrate 146 to a chelating agent in solution to remove excess nickelion from the surface. In this way, stray uncoordinated nickel ion doesnot coordinate to the self-assembled monolayer 148 at regions outside ofthose regions to which carrier 142 and 144 had been applied. Thelatter-applied chelating agent preferably less-strongly coordinatesnickel ion than the chelating agent immobilized at the surface.Following this application step, a, plurality of isolated regions ofself-assembled monolayer 148 include nickel ion. Accordingly, when thesurface is exposed to a polyamino acid-tagged biochemically activeagent, the biochemically active agent will attach selectively at thoseregions to which nickel ion had been applied.

According to another embodiment, self-assembled monolayer 148 can be aspecies X-R-Ch-M as described in the above-referenced co-pendingapplication Ser. No. 08/312,388, and the species 142 and 144 can bepolyamino acid-tagged biological binding partners, optionally containedin a fluid carrier, that are attached to the surface selectively atthose regions corresponding to the indentation pattern of theapplicator. According to this embodiment the separate, isolated regionscan include separate, distinct biochemically active agents. This can beaccomplished, for example, by placing applicator 136 in register with aplurality of reservoirs of distinct (different) biochemically activeagents to position distinct biochemically active agents in therespective indentations of the applicator, then placing the applicatoradjacent the surface of substrate 146 to transfer distinct biochemicallyactive agents to distinct, isolated regions of the surface. Theprocedure can be repeated using fresh substrate surfaces for each step,thus surfaces carrying distinct regions of distinct biochemically activeagents can be mass produced. In addition to the species described above,cells can be immobilized at a substrate surface in this manner as well.Register between the applicator and the substrate surface can becontrolled via mechanical, electronic, magnetic, and/or opticalapparatus.

According to another embodiment, species 142 and 144 or species carriedby fluid carriers 142 and 144 can be transferred to a surface carrying aself-assembled monolayer other than the monolayer of X-R-Ch-M asdescribed above. For example, a self-assembled monolayer exposing ahydrophobic functionality such as an alkane functionality can be formedon a surface (e.g., hexadecanethiol on gold) and a biochemically orchemically active agent that adheres to a hydrophobic surface can thenbe applied to the surface in discrete regions or in a pattern asdescribed above. Where the biochemically active agent is a cell orcells, it may be advantageous to coat the hydrophobic surface with acytophilic species such as laminin. Reference can be made to U.S. patentapplication Ser. No. 08/131,838 of Sighvi, et al. referenced above, inconnection with the immobilization of cells at surfaces.

Immobilization of cells and other biochemically active species can becarried out without a self-assembled monolayer as well. For example, ahydrophobic surface coated with laminin, and free of self-assembledmonolayer, can serve as a substrate for immobilization of a pattern ofcells in accordance with the invention.

According to this and other embodiments, the substrate surface can carrychelating agent immobilized via other than a self-assembled monolayer.For example, chelating agents coupled to dextran at a surface, as isknown, can be employed. Although a self-assembled monolayer 148 isillustrated on the surface of substrate 146, a self-assembled monolayeris not needed according to all embodiments. For example, substrate 146can be adhesive to a species transferred to it from applicator 136, forexample a biochemically or chemically active agent and fluid carriers142 or 144, or the like. Additionally, the applicator can be placed incontact with the substrate surface and allowed to remain in place whileany species present in the fluid precursor is allowed to harden, thefluid carrier is allowed to dissipate, or the like.

In accordance with all embodiments of the invention, such as thoseillustrated in FIGS. 1, 2, and 11, the species formed proximate thesubstrate surface in a pattern corresponding to the indentation patternof the article itself can be a self-assembled monolayer. Suitableself-assembled monolayer-forming species are described in U.S. Pat. No.5,512,131 of Kumar, et al., referenced herein. Self assembled monolayersformed of species X-R-Ch, as described above, with or without metal ionand/or biological species coordinated thereto, can be used, as well asother self-assembled monolayer-forming species disclosed in applicationSer. No. 08/312,388, by Bamdad, et al., referenced above.

FIG. 12 illustrates schematically a process for applying a species fromindentations in an applicator to a non-planar surface. An applicator 136(shown in cross section) includes a plurality of indentations 138, eachfilled with a species 150. Each of the indentations can be filled withthe same fluid or different fluids. Species 150 can be any of theabove-described fluid precursors, chemically or biochemically activeagents, or the like. An article 152 having a surface 154 is placedadjacent the application surface of applicator 136 and rolled againstthe applicator as described in commonly-owned, co-pending U.S. patentapplication Ser. No. 08/397,635 by Whitesides, et al., entitled“Microcontact Printing on Surfaces and Derivative Articles”, andInternational Patent Application Publication No. WO 96/29629, bothincorporated herein by reference. As the article 152 including nonplanarsurface 154 is rolled against the applicator 136, species 150 istransferred to surface 154 in a pattern corresponding to the indentationpattern of the applicator. The indentation pattern can be any pattern asdescribed above, for example individual, isolated regions or one or morecontinuous linear or non-linear indentations. The indentation orindentations can be of one or more depths. Application to nonplanarsurfaces having various radii of curvature can be carried out accordingto the invention, for example, radii of curvature of less than about onecentimeter, preferably less than about one millimeter, more preferablyless than about 500 microns, more preferably less than about 100microns, more preferably less than about 50 microns, and according to aparticularly preferred embodiment printing can occur on substrates withradii of curvature on the order of about 25 microns or less.

FIG. 13 illustrates an article 154 created by forming, on a silicondioxide surface 156 of a silicon substrate 158, a patterned structure160, for example a polymeric structure formed from a prepolymeric fluidusing a micromold as illustrated in FIG. 1. Subsequently, a second fluidprecursor is positioned so as to cover the patterned structure 160 andallowed to solidify. According to the embodiment illustrated, a fluidprecursor was placed atop the patterned structure 160 and a micromoldhaving a complex pattern was placed atop the fluid precursor. The fluidprecursor was hardened to form a structure 162 covering and encompassingthe patterned structure 160 on the substrate surface. The secondstructure 162 included an exposed surface 164 having a pattern ofindentations 165 complementary to the indentation pattern of the secondmicromold. The overall structure, when structure 160 differs inrefractive index from structure 162, can serve as a waveguide, thesecond structure 162 serving as a cladding. The contoured surface 164 ofcladding 162 is lossy. The pattern of surface 164, in most instances, isnot important to the waveguide function. Waveguides were fabricated fromseveral classes of polymeric materials (epoxies, polyurethanes, andpolyacrylates on Si/SiO₂ substrates. Waveguides clad with polymershaving slightly lower refractive indices gave single-mode output in thevisible and near infrared regions. A typical waveguide structureexhibiting single-mode behavior consisted of a trapezoidal waveguide(n_(guide)=1.545) clad in a polymeric slab with n_(cladding)=1.52. Thewaveguide was 0.7 centimeters long and the wavelength of light was 0.85micron. Photocurable polymers are preferred. Waveguides are described ingreater detail below.

Referring now to FIGS. 14a-k, a schematic illustration of a surfacederivatized so as to include discrete regions of differing chemicalfunctionality is shown. The article schematically illustrated findsparticular use as a combinatorial library. An article by Jacobs, et al.,entitled “Combinatorial Chemistry-Applications of Light-DirectedChemical Synthesis”, Trends in Biotechnology, volume 12, 19-26 (January,1994; incorporated by reference above) describes a photolithographicprocess for forming a combinatorial library. Jacobs, et al. describederivatizing a substrate with linker molecules that contain aminesblocked by a photochemically cleavable protecting group. Specific siteson this synthesis surface are photo-deprotected by illumination througha photolithographic mask. Those regions exposed to light aredeprotected, and may then be coupled to amino acids of interest usingstandard peptide-synthesis conditions. The process is repeated using newmasks until an array of compounds of the desired length and compositionare built up. The patterns of photolysis and order of addition of aminoacids define the products and their locations on the solid support. Thepresent invention can find application in combinatorial librarysynthesis with a minimum of expense and equipment. Those of ordinaryskill in the art will recognize that any of a wide variety of chemicallyand biologically active agents can be used in accordance with theprocedure discussed below and illustrated in FIGS. 14a-k. The criteriafor selection of such agents is similar to selection criteria for thoseagents described above that can be positioned on a substrate surfaceusing a forming article or micromold 20. In a manner analogous to theprocedure of Jacobs, et al., wet chemical protecting groups can beutilized in accordance with the present invention rather thanphotochemically cleavable protecting groups. Orthogonal-stripe methodsand binary synthesis of combinatorial libraries in accordance with theinvention, with reference to FIGS. 14a-k, are described below in theprophetic example.

The following prophetic example involves the creation of a combinatoriallibrary on a substrate surface using the micromold of the invention.With optional reference to Jacobs, et al., “CombinatorialChemistry-Applications of Light-Directed Chemical Synthesis”, Trends inBiotechnology, 12, 19-26 (January, 1994) and Chemical & EngineeringNews, 74, 7, 28-73 (Feb. 12, 1996), those of ordinary skill in the artcan follow the teachings herein to form a combinatorial libraryinexpensively.

Reference will be made to FIGS. 14a-k, which illustrate schematicallytop views of a substrate surface. FIGS. 14a-c illustrate an“orthogonal-stripe” method. According to the technique, a plurality ofmicromolds are fabricated, each of which has a distinct channel pattern.Each micromold is fabricated so as to cover substrate surface 166, or atleast enough of substrate surface 166 to define a channel or channelsnecessary for application of chemically or biochemically active agentsto desired regions of the surface. For purposes of illustration, thedescription will assume use of a micromold that completely coverssubstrate surface 166, and includes indentations in register withcertain portions of substrate surface 166. One micromold includes anindentation in register with a portion of the substrate surfacedesignated “A” in FIG. 14a and includes a contact surface that contactsthe remaining substrate surface at areas designated “B”, “C”, and “D”.With reference to FIG. 14b, individual micromolds will be fabricatedthat include contact surfaces that cover all portions of the substrateexcept one of the portions “E”, “F”, “G”, or “H”. That is, eachmicromold forms a channel through which a chemically or biochemicallyactive agent (reactant) can be delivered to the substrate surface at aportion in register with the channel, while remaining portions of themicromold block regions proximate the substrate surface from interactionwith the particular chemically or biochemically active agent. Anycombination of micromolds can be used to apply to the surface, in anycombination, various chemically or biochemically active agents. Forexample, with reference to FIG. 14a, if a micromold having a channel inregister with region “A” of the substrate surface is used to apply tothe surface a chemically active agent “A” and then, with reference toFIG. 14b, a micromold is placed adjacent the substrate surface that hasan indentation in register with region “E” and is used to apply toregion “E” a chemically active agent “E”, the substrate surface willinclude a region carrying chemically active agent “A” (the regiondesignated “A” in FIG. 14a), a region carrying chemically active agent“E” (the region designated “E” in FIG. 14b), and at the region where theregions “A” and “E” intersect both chemically active agents will havebeen applied (upper left corner of the substrate surface as viewed inFIG. 14c). It can be seen that, if all combinations of micromolds andchemically active agents are employed, the result will be a grid on thesubstrate of each combinatorial permutation of the chemically activeagents each confined to a separate region of the substrate surface (FIG.14c). As is apparent to those of ordinary skill in the art, the order ofapplication of active agent to the various regions of the substratesurface can be used to tailor the synthesis of the individual species atthe various locations on the substrate surface.

With reference to FIGS. 14d-k, a “binary” synthesis technique isdescribed. In FIG. 14d, a first micromold having an indentation inregister with region “A” and a contact surface in register with region“Ø” is used to apply to the substrate surface an active agent “A”selectively at region “A”. FIG. 14b shows surface 166 including a region“B” in register with an indentation of a second micromold and a region“Ø” in register with a contact surface of the second micromold, viawhich an active agent “B” can be applied selectively to region “B” ofthe substrate surface. FIG. 14f shows surface 166 having portions “C”and “Ø” that are positionable in register with indentations and contactportions, respectively, of a third micromold to apply an active agent“C” to regions “C”. In FIG. 14g the surface includes portions “D” and“Ø” that are positionable in register with indentations and contactportions, respectively, of a fourth micromold to transfer agent “D”selectively to regions “D”. The binary technique is less labor intensivethan the orthogonal-stripe method in that only four transfer or flowsteps involving four micromolds are needed to create a grid of sixteendistinct chemically or biochemically functional regions on the substratesurface.

After application of the first micromold and formation of chemically orbiochemically active agent “A” via the channel of the first micromold,agent “A” is applied to the left side of the substrate surface 166 andthe right side of the substrate surface remains free of agent asillustrated in FIG. 14h. After application of agent “B” to the upperportion of substrate surface using the second micromold, four quadrantsof the substrate surface carry agent “A” plus agent “B”, agent “B”,agent “A”, and no agent, respectively, as illustrated in FIG. 14i. Afterapplication of agent “C” via the channels of the third micromold, eightregions of distinct chemical or biochemical functionality exist on thesurface as illustrated in FIG. 14j. After application of agent “D” viathe indentations of the fourth micromold, sixteen distinct chemically orbiochemically active regions are formed as illustrated in FIG. 14k,namely “ABCD”, “ABC”, “BCD”, “BC”, “AND”, “AB”, “BD”, “B”, “ACD”, “AC”,“CD”, “C”, “AD”, “A”, “D”, and “Ø”. The register between each micromoldand the substrate surface can be controlled by pins in the substratethat engage each micromold, pins in each micromold that engage thesubstrate surface, an X-Y table that positions the substrate surfaceidentically relative to each micromold, optical, magnetic, or electronicaligning apparatus, or other equivalent apparatus that can align eachmicromold with the substrate surface. Accurate register at the micronscale is achieved.

Those of ordinary skill in the art have the ability to select, withoutexperimentation or with only routine experimentation, chemically orbiochemically active agents that can be used to create a myriad ofchemically active or biochemically active combinatorial librariesaccording to the technique of the invention. It can be useful to firstcoat substrate surface 166 with a common chemical linker functionalitycoupled to a chemical protecting group, apply a first micromold to thesubstrate surface, first deprotect at the region in register with thechannel, then carry out a synthesis step at that region and reprotect,then remove the first micromold and apply a second, different micromold,again deprotect at the portion of the substrate surface in register withthe channel of the second micromold, carry out a second synthesis step,and reprotect, etc. Libraries of peptides, synthetic molecules such asnew drugs, naturally-occurring chemical and biochemical species,oligonucleotides and the like can be created. Indeed, any of thechemically or biochemically active agents, fluid precursors,prepolymeric fluids, or the like as described above that aretransferable from a microapplicator or that can be applied, for examplevia capillary action, to a surface using a micromold as described above,can find use in the combinatorial arrangement described. Any combinationof various agents can be used.

As an alternative embodiment to that described above, an article 20 asillustrated in FIG. 2, having a contoured surface 22 including aplurality of protrusions separated by intervening indentations 24 can beused as a stamp for forming a combinatorial library. Stamping asdescribed in U.S. Pat. No. 5,512,131 (issued Apr. 30, 1996 to Kumar, etal., referenced above) can be employed. The stamp includes a stampingsurface defined by the outer surfaces of the protrusions. The process isdescribed with reference to FIGS. 14d-k. A surface 166 carries aprotecting group, for example, a self-assembled monolayer exposingoutwardly an azide functionality. A stamp having a surface including aprotrusion in register with area A of surface 166 (FIG. 14d) is preparedby applying to the protrusion a deprotecting species such as a reducingagent for reduction of the azide to a deprotected, reactive amine.Application of the stamp to surface 166 deprotects the self-assembledmonolayer at region A, but leaves the remainder of surface 166 (Ø)protected. Then, chemical reactivity at region A can take place,followed by reprotection of the entire surface. Then the stamp can bere-oriented, or a second stamp chosen, so that region B is deprotectedby contact with a stamping surface (protrusion) of a stamp. Chemicalreaction then is carried out a region B, and the surface re-protected.With reference to FIG. 14f, a stamp having protrusions corresponding toregions C is used to deprotect at regions C, followed by chemicalreaction at regions C and re-protection, and the process carried outsimilarly at regions D (FIG. 14g). According to a preferred embodiment,the stamping surface itself, without any auxiliary agent carriedthereon, can deprotect at regions of surface 166 in register with thestamping surface. For example, a stamp having an acidic stamping surfacesuch as a hydrogel loaded with a component of low pH can be used. Forexample, Dextran™ carrying polyphosphoric acid can be grafted to asurface of a rigid or elastomeric stamp and used to deprotect surface166 at regions corresponding to the protrusions or stamping surface.Other protecting/deprotecting chemistries such as hydrolysis chemistrycan be carried out.

According to another embodiment, rather than building a combinatoriallibrary through step-by-step synthesis of various species at variousdistinct regions proximate a substrate surface, distinct species can besynthesized and applied to the substrate surface after synthesis. Acombination of these approaches can be used as well, involving synthesisof building blocks that are assembled according to the propheticexample.

FIG. 15 illustrates a set of particularly preferred fabricationtechniques of the invention in which, rather than applying article 20 tosubstrate surface 28 followed by introduction of fluid precursor 36 intochannels 32 so defined, article 20 is used as an applicator to transferthe fluid precursor to substrate surface 28. The following descriptionwill be made with reference to fabrication of a structure 38 and otherstructures that are waveguides, from a precursor 36 that will bereferred to as a waveguide precursor, although the following descriptiondefines one aspect of the invention that is applicable to creation ofany of a wide variety of structures described herein and is not limitedto waveguides. In FIG. 15, fluid precursor 36 is first applied toindentations 24 of applicator 20. Excess fluid precursor then can beremoved, by scraping, from application surface 22. For example, a blockof material similar or identical in composition to that of article 20can be used to scrape off excess prepolymer. Alternatively, withappropriate structures, the excess precursor can be blown off with abrisk stream of gas such as nitrogen. A brisk stream of gas also can beused to remove remaining drops of precursor after the bulk excess ofprecursor has been scraped away. Applicator surface 22, the indentationsof which are filled with fluid waveguide precursor 36, then is placed incontact with surface 28 of substrate 30. Applicator 20 then can beremoved, leaving some or all of precursor 36 in contact with surface 28where it is subsequently made dimensionally stable or, according topreferred embodiments, fluid precursor 36 is hardened to the point thatit is dimensionally stable while article 20 remains in place uponsubstrate surface 28. Where fluid precursor 36 is a fluid prepolymer,and is heat-curable, the precursor can be heated, for example, byheating substrate 30, article 20, both substrate 30 and article 20, orapplying radiative heat. Where precursor 36 is a photopolymerizablefluid, it can be exposed to electromagnetic radiation that causespolymerization. A fluid precursor 36 can be partially or fullypolymerized prior to removal of article 20, so long as it is polymerizedto the extent that it is dimensionally stable and self-supporting. Inpreferred embodiments, as described below, it is often advantageous toonly partially polymerize a fluid prepolymeric precursor 36.

Where fluid precursor 36 is a fluid carrier of a suspension, the fluidcarrier can be selected in conjunction with the material of article 20to allow the fluid to be absorbed into article 20 and therebydissipated, resulting in deposition of solid material from thesuspension as the patterned material on substrate surface 28. Wherefluid precursor 36 is a solution of a dissolved precipitating species,conditions such as temperature, pH, or the like can be altered to causeprecipitation. One advantage of the technique of FIG. 15 is that thefluid precursor is in contact with article 20 for only a very briefperiod of time, thus if article 20 adsorbs or absorbs any components offluid precursor 36 disadvantageously, such as adsorption of dyes, thisis minimized. Another advantage is that with a thermally-curableprecursor the technique is made much easier since the time required forthe process is very fast relative to typically curing times.

Following solidification of fluid precursor 36 to form an array ofwaveguides 38, solidification taking place to the extent that waveguide38 is dimensionally stable, article 20 is removed from substrate 30.Following this step, or other steps for forming an array of waveguides38 on substrate surface 28 (e.g. as described with reference to FIG. 1),a cladding can be provided upon the waveguide array to form a waveguideassembly 44 by adding a hardenable cladding precursor fluid 40 on top ofthe array, optionally forming fluid 40 into a desired shape with adesired thickness above and beside the waveguide array by, for example,positioning a cladding mold 42 above the precursor to form theprecursor, allowing the cladding precursor to harden (for example, viapolymerization) and removing cladding mold 42 to form a cladding 43 thatincludes a layer of cladding above waveguides 38. In another embodimenta cladding mold 168 can be used which molds cladding precursor 40between waveguides 38 and laterally of waveguides 38, but does not allowformation of cladding above the waveguides to form an assembly 172. Thiscan be accomplished where the cladding mold 168 is a flexibleelastomeric mold that conforms to form a mold resting atop waveguide 38.The cladding precursor is allowed to harden, and removal of the moldresults in a cladding 170 that fills spaces between waveguide 38, andextends laterally beyond the lateral-most waveguides such that each sideof each waveguide is contacted by cladding, but the top of eachwaveguide is exposed. In another embodiment a waveguide assembly 174 canbe formed by applying cladding precursor 40 to waveguides 38, allowingthe cladding precursor to drip off of the waveguides, and hardening thecladding precursor.

In each case, subsequently, the substrate/waveguide/cladding assemblycan be cleaved along lines a—a and b—b to define a waveguide assembly44, 172 or 174 having a typical waveguide width x on the order of lessthan about 100 microns, typically on the order of from about 1 to about10 microns, more typically from about 2 to about 4 microns, a waveguideheight y on the order similar to that of dimension x, more typicallyslightly less than x, for example about 1 micron, and, in the case ofwaveguide assembly 44, an overall assembly height including cladding ofa dimension z on the order of dimension y to about 10 times dimension y,for example from about 1 to about 10 microns and a length 1 of any of awide variety of lengths on the order of 100 microns to centimeters.Larger waveguides can be made as well, for example waveguides havingwidth or height on the order of 200 or 250 microns, with spacing ofsimilar order. In the case of waveguide assembly 172 the cladding heightequals the waveguide height, and in the case of 174 the cladding heighttypically is very slightly greater than the waveguide height.

Another technique for fabricating a waveguide assembly 172, includingwaveguides 38 and cladding 170 which contacts the sides, but not thetops of waveguides 38 is as follows. Following fabrication of waveguides38, and prior to application of any cladding, a microcontact printingtechnique as described in international patent publication no. WO97/07429, of international patent application no. PCT/US96/13223entitled “Patterned Materials Deposition Effected with MicrocontactPrinting” is carried out to apply a hydrophobic component selectively tothe tops, but not the sides of waveguides 38, followed by addition of ahydrophilic cladding prepolymeric precursor which assembles within andbetween waveguides 38, but not atop waveguides 38, followed by curing ofthe cladding precursor. The particular microcontact printing techniqueinvolves coating a flat applicator with a self-assembled monolayerforming molecular species and applying the flat applicator to waveguides38 such that the applicator contacts only the tops of waveguides 38. Anymolecular species transferable in this manner can be used to create ahydrophobic functionality atop waveguides 38 such that a hydrophilicprepolymer will assemble between waveguides 38 and laterally on eitherside, or the opposite can be carried out in which a hydrophilic materialis applied to the tops of waveguides 38 and a hydrophobic claddingprecursor used to fill spaces between and laterally of the waveguideswhere the waveguides and surface 28 of substrate 30 is sufficientlyhydrophobic. In one technique, surface 28 and waveguides 38 weresubjected to oxidizing treatment, and microcontact printing was used totransfer a self-assembled monolayer of a fluorine-terminating moleculeto the surface. Specifically,tridecafluoro-1,1,2,2-tetrahydro(o-octyl)-1-trichlorosilane was appliedto the tops, but not sides, of waveguides 38 and formed a hydrophobicself-assembled monolayer thereon. A hydrophilic cladding precursor, inparticular a liquid polyurethane prepolymer, was added and assembledbetween and laterally of waveguides 38. Curing of the polyurethanecladding precursor, followed by cleaving of the waveguide ends, resultedin a waveguide assembly similar to assembly 172.

In typical embodiments, cladding is added to waveguides 38 to lower therefractive index difference between waveguides 38 and their surroundingenvironments. Without cladding, waveguides 38 typically are very goodperformers, but support too many modes. Addition of cladding, whichreduces the refractive index difference at the boundaries of waveguides38, reduces higher order modes.

FIG. 13 (discussed above) is essentially identical to a cross-sectionthrough line a—a of waveguide assembly 44 of FIG. 15, showing a typicalsubstrate 30, optional film 31 of an adhesion promoter, native oxidelayer, or the like on substrate 30 (the top surface of film 31 definingsubstrate surface 28 according to this embodiment), array of waveguides38, and cladding 43. The waveguide of FIG. 13 differs from waveguidesfabricated in accordance with the technique of FIG. 15 in that itincludes a contoured cladding surface corresponding to a contouredcladding mold. Precursor 36 is a material as described above which canserve as a waveguide. Selection of such materials is within the level ofordinary skill in the art.

In embodiments of the invention involving waveguide fabrication,substrate 30 can be essentially any material including those materialsdescribed above, but should be optically smooth. Substrate surface 28can be of the same material as the bulk material of substrate 30, or adifferent material. A non-limiting, exemplary list of substratematerials includes silver, gold, glass, silicon/silicon dioxide, and thelike. The waveguide pattern can be formed on contoured surfaces, andflexible surfaces. Where substrate 30 is flexible (for example, apolyvinylchloride film) the waveguide can be deformed while guidinglight. The utility of this technique will be described more fully below.In embodiments of the invention involving waveguide fabrication, article20 can be as described above, and preferably is elastomeric.

Selection of materials for waveguide 38, cladding 43, and substrate 30(and optional film 31) can be selected by those of ordinary skill in theart to form a structure that can guide electromagnetic radiation of adesired frequency. As is known, total internal reflection ofelectromagnetic radiation will occur within waveguide 38 where theelectromagnetic radiation propagating within the waveguide strikes aninterior boundary of the waveguide to form an angle θ, with a linenormal to the interior boundary, where sin θ is ≧(refractive index ofthe cladding)/(refractive index of the waveguide). Those of ordinaryskill in the art can select materials to form the overall system 44 thatwill serve as a waveguide. In one set of embodiments cladding 43 can benon-existent. That is, the cladding can be the environment surroundingthe waveguide, such as air. In some embodiments it is useful to have acladding defined by a material filling the indentations between anddefined by waveguides 38, where the top surfaces of waveguides 38 areexposed to ambient conditions. The difference in index of refractionbetween waveguide and cladding, and waveguide and the substrate,typically is from about 0.01 to about 0.001. These and other embodimentscan be useful as sensors, etc., and are described more fully below.

It is one feature of the invention that waveguides 38 and cladding 43can be formed from an identical, or nearly identical fluid prepolymer,the degree of polymerization of which can be controlled by the amount ofexposure to polymerization conditions such as heat or radiation. Forpurposes of the invention, “polymerization” is meant to encompasscross-linking. This technique is facilitated by the fact that therefractive index of a solid typically is greater than the refractiveindex of a liquid of similar composition in that the density of a solidtypically is greater than of a liquid. The difference in index ofrefraction typically decreases with curing time for a polymer. Thus, thedifference in refractive index can readily be tailored. This techniqueprovides several advantages that will become apparent from thediscussion below. One advantage is simplicity, since in this embodimentonly a single prepolymer fluid need be used, first as prepolymer fluid36 (with reference to FIG. 15) that is positioned with article 20against substrate surface 28 and polymerized, for examplephotopolymerized, followed by addition of a common prepolymer (the sameprepolymer) cladding precursor 40 which then can be photopolymerized.During polymerization (curing) of cladding prepolymer 40, waveguide 38is cured to a greater extent, and the refractive index differencebetween cladding 40 and waveguide 38 decreases during curing of cladding40. One advantage of using identical, or nearly identical fluidprepolymers both for waveguides 38 and cladding 43, the difference inrefractive index being due to different curing times, is that airbatch-to-batch difference between polymers is unimportant as the amountof exposure to polymerization conditions is the only important feature.That is, the relative refractive index change in material, duringcuring, is what is important, and conditions do not need to be adjustedbecause of slight variation in material composition.

One advantage of the transfer technique of FIG. 15 is that it isexceptionally simple experimentally, and very inexpensive. It canreadily be used to produce multiple copies of complex microstructures.Another advantage of the technique is that many waveguides can befabricated essentially simultaneously. Tens or hundreds of applicators20 can be fabricated from a single master which is, in turn, fabricatedfrom a photolithographically created surface or the like, and eachapplicator can be used to fabricate hundreds or thousands of waveguides.For example, where an applicator 20 having a dimension perpendicular tothe linear dimension of indentations 24 of approximately 3 centimetersis used, and indentations 24 each are of approximately 2 microns inwidth and spaced approximately 2 microns from each other, one moldingprocess as illustrated in FIG. 15 can result in more than 4,000waveguides.

Another advantage of the transfer molding technique of FIG. 15 is thatmultiple layers of waveguides can be fabricated readily. With referenceto FIG. 16, applicator 20 first can be used to transfer fluid waveguideprecursor 36 to substrate surface 28 where it is hardened to formwaveguide array 38, as illustrated also in FIG. 15, and then waveguidearray 38 on substrate 30 can be placed upside down upon anotherapplicator 20 including indentations filled with fluid waveguideprecursor 36, precursor 36 can be cured, and applicator 20 removed toform a two-layer stacked array 248. The process can be repeated anynumber of times to form any number of layers of waveguide arrays, asexemplified by stacked waveguide array 250, with the waveguides arrangedin any orientation relative to each other in which support for eachlayer is provided.

Yet another advantage is that periodicity in the cladding structure 43(FIG. 15) can be readily formed, via a cladding mold 42 including aperiodically contoured inner surface, or via irradiation of cladding 43through a mask to cure alternating portions of the cladding to a greaterextent relative to intervening portions. In this manner, a grating canbe fabricated in the cladding, such as a Bragg grating. Gratings alsocan be fabricated directly in or onto waveguides 38 by using a mold 20in which the indentations that in part define the mold for thewaveguides includes a contoured interior surface. Chirped waveguides andother periodic structures can be fabricated in the cladding, or in thewaveguide core itself, in this technique. Attenuation can be achieved inthis way, and resident cavities can be created.

Another feature of the present invention is the ability to fabricatewaveguide couplers, easily and conveniently, regardless of the localgeometry of the waveguide. FIG. 17 is a schematic illustration of aprior at “Y” coupler including branched portions as shown, for example,in U.S. Pat. No. 5,313,545 (Kuo, et al.), including a coupling region252 and branching input/output regions 253, 254, 255, and 256. Radiationinput from regions 253 and 255 will couple at region 252 and will branchand travel along both branching portions 254 and 256. Alternatively,radiation input from branches 254 and 256 can be made to couple atregion 252 and branch into regions 253 and 255, optionallyconstructively or destructively interfering to some extent in region252.

FIG. 18 is an illustration of a prior art “evanescent” coupler, theprinciple of which is used to provide coupling between guides of U.S.Pat. No. 5,481,633 (Mayer). This coupler operates on the principle that,depending upon the refractive index between waveguide and surroundingenvironment (e.g., cladding) the waveguide dimensions (size and shape),the wavelength of light, and separation between waveguides, an“evanescent tail” extends from each waveguide, the energy of the taildecreasing with distance from the guide. Where waveguides are closeenough to each other, and the evanescent tail passes into the adjacentwaveguide, radiation can leak into the adjacent waveguide and thewaveguides couple. In the prior art array of FIG. 18, waveguide 258includes a coupling portion 260 and non-coupling portions 262 and 264and waveguide 266 includes a coupling portion 268 and non-couplingportions 270 and 272. In the array illustrated, based upon the selectionof materials and dimensions and wavelength of light, coupling portions260 and 268 are close enough such that the evanescent tail of radiationin each guide passes into the adjacent guide and coupling occurs inthese regions. However, non-coupling portions 262, 264, 260, and 272each are separated from the adjacent waveguide by a distance that doesnot allow coupling. Coupling thus controllably occurs only at regions260 and 268, which thereby defines a coupling junction. The prior artarrays of FIGS. 17 and 18 are suitable for many purposes, but, as can beseen, requires significant control and geometry of construction.

The particular shape of the waveguide required for either of thecouplers of FIGS. 17 and 18 is limited also by the fact that curves orcorners that form part of the shape of a waveguide should not exceed amaximum amount of sharpness, or the critical angle of total internalreflection will be exceeded and loss of electromagnetic radiation willoccur.

The invention provides a solution to this problem, as illustrated inFIG. 19 which illustrates an array including essentially parallelwaveguides 274 and 276 and cladding 278 which can completely envelopeand cover waveguides 274 and 276, or the like. Each of waveguides 274and 276 and cladding 278 can be formed from an identical prepolymericprecursor with differences in refractive index controlled by differentcuring times. The array of waveguides 274 and 276 and cladding 278includes central portion 280 and lateral portions 282 and 284. Curingtimes are controlled such that the refractive index ratio betweenwaveguides 274 and 276, and cladding 278, within central portion 280 isrelatively small, while the refractive index ratio between thewaveguides and the cladding in lateral portions 282 and 284 isrelatively high, such that coupling occurs between waveguides 274 and276 within portion 280, but does not occur in lateral portions 282 and284. Thus, region 280 defines a coupled region of the waveguides that isfunctionally similar to the coupled portions 260 and 268 of waveguides258 and 266 of FIG. 18, and coupled portion 252 of the branchedstructure of FIG. 17. This can be achieved, for example, as follows.Waveguides 274 and 276 are fabricated from fluid polymeric precursors asillustrated in FIG. 15, and only partially cured to the extent that theyare dimensionally stable. Then, the same polymeric precursor, as acladding precursor, is placed over waveguides 274 and 276 and cureduntil dimensionally stable. Where the refractive index difference atthis point in the process is great, coupling cannot occur through all ofportions 282, 280, and 284 of the array. Subsequently, only portion 280is subjected to additional photopolymerization conditions, resulting insignificantly decreased refractive index differences between waveguides274 and 276 and cladding 278 in that region (280). The result is that,in regions 282 and 284, coupling does not occur, but in region 280coupling occurs. One advantage of the technique is that coupling can betailored at any region of the waveguide array where waveguides designedto carry UV or visible light, of the type produced by a red He—Ne laser,are separated more than about 2 microns, for example up to 6 microns, 8microns, or even 10 microns in region 280, allowing much simplerfabrication that does not require as much precision. In contrast, thecoupling regions of FIG. 18 are defined by their separation distance,which typically must be much smaller than the separation distanceallowable for the system of FIG. 19, requiring significantly greaterprecision and related expense.

In another embodiment of the invention the locations of the regions ofcoupling between waveguides are tailorable, and the amount of couplingat those locations is controllable. This can be accomplished whenwaveguides 274 and 276 and cladding 278 are selected such that therefractive index ratio between waveguide and cladding can be changed,reversibly, after fabrication. For example, where the refractive indexof cladding 278 can be changed reversibly based upon exposure tospecific electromagnetic radiation (where, for example, cladding 278 isreversibly photosensitive; such materials are known to those of ordinaryskill in the art) the array can be fabricated and region 280 irradiatedwith the specific radiation to cause coupling where no coupling occursin regions 282 and 284. Then, the specific radiation can bediscontinued, terminating coupling in region 280, and region 282 can beexposed to the specific radiation resulting in coupling within region282 where no coupling occurs in regions 280 and 284. As can be seen acoupling pattern in a large array can be readily changed, reversibly,depending upon the pattern of the specific radiation. In anotherarrangement, cladding 278 can be one or more fluids contained inseparate chambers that define regions 280, 282, and 284, and the contentof the fluid chambers can be controlled to control the refractive indexratio between waveguide and cladding.

The above technique facilitates a waveguide coupler that can be used atdifferent wavelengths of light. That is, where the refractive indexdifference at the boundaries of waveguides can be adjusted during use,or between uses, by exposure to different electromagnetic radiation,electric fields, or the like, the waveguide can be adjusted for use withdifferent wavelengths of light. This also can be used to adjust thedegree of coupling that occurs during use. For example, coupling couldbe adjusted from ten percent to fifty percent by exposure toelectromagnetic radiation according to this technique.

The geometrical tailorability of refraction index ratio between claddingand waveguide facilitates the creation of a variety of switches andsensors. With reference to FIG. 19, where cladding 278 is anelectro-optical material or other material that can reversibly changerefractive index upon exposure to certain electric fields, or is anon-linear optical material (e.g., dye) that changes in refractive indexin response to electromagnetic radiation, the array can be a sensor ofthat electric field or electromagnetic radiation since exposure to thefield or radiation will cause a detectable change in coupling betweenwaveguide 274 and waveguide 276. In one arrangement, region 280 can bedefined by a cladding that is reversibly electric field sensitive, whilesections 282 and 284 are not, thus sensitivity to the specific electricfield exists at region 280 only, and coupling at region 280 isindicative of the existence and strength of the field.

As an example of a sensor of a chemical or biological species inaccordance with the invention, the cladding of region 280 can include,on its exposed surface, a material that is sensitive to a particularanalyte such that when the analyte is present, the refractive index ofthe cladding changes in an amount sufficient to detectably change thecoupling characteristic between waveguides 274 and 276 in region 280. Asone example, region 280 can define a flow chamber about waveguides 274and 276 such that a desired fluid can be reversibly placed in contactwith waveguides 274 and 276 in region 280. The change in the existenceof, or concentration of, a particular analyte in the fluid (such as asalt or other refractive index-altering substance) can causequantitative, or qualitative changes in coupling between guides 274 and276 at region 280, resulting in quantitative or qualitative sensing. Forexample, a cation or anion exchange material can be provided that asurface, such as a sulfonic, phenolic, phosphoric, or carboxylic acidgroup, for capture of ions from solution. Chelating agents, kryptands,crown ethers, and the like can be used.

As another example, the array of FIG. 19 can be constructed where, atregion 280 (or other or all regions) cladding 278 includes an exposedsurface that carries an immobilized biological binding partner of abiological molecule or exposed surfaces of waveguides 274 or 276 carryan immobilized biological binding partner. Referring to FIG. 15, where atechnique for forming a very thin cladding on the waveguides is used,the biological molecule can be provided on the cladding. A moresensitive sensor can result from a waveguide fabricated, with referenceto FIG. 15, including exposed top surfaces. In a method for sensing thebiological molecule, a medium suspected of containing the biologicalmolecule is exposed to the surface of cladding 278, waveguide 274 and/or276 (at region 280) if region 280 carries the biological binding partnerexclusively and, if present, the biological molecule binds to itsimmobilized binding partner, changing the refractive index of cladding278 (e.g. at region 280) and thereby changing the refractive index ratiobetween the waveguides and cladding in that region, detectably alteringcoupling. As mentioned, where a cladding completely covers waveguides274 and 276 in this particular embodiment, it is generally desirablethat cladding 278 form only a very thin layer above waveguides 274 and276, such that biological binding at the outermost surface of thecladding produces a greater relative effect in change of refractiveindex ratio between waveguide and cladding. Alternatively, the claddingmay be non-existent and the biological molecule can be immobilizeddirectly upon a surface of the waveguide, or the cladding can partiallycover the waveguide surface with remaining portions of the waveguidesurface carrying the immobilized binding partner. In specificembodiment, any of a variety of biological binding pairs can be used,one member of the pair immobilized at cladding 278 or waveguides 274 and276 and the other member being the analyte. In this context, the term“biological binding pairs” is as defined above, referring to acorresponding pair of molecules that exhibit mutual affinity or bindingcapacity, typically specific or non-specific binding or interaction,including biochemical, physiological, and/or pharmaceuticalinteractions.

As mentioned above, substrate 30 can be flexible. This facilitates amethod involving guiding electromagnetic radiation through a waveguidearray of at least two waveguides, simultaneously, while altering theconformation of the waveguides. That is, the substrate carrying aplurality of waveguides can be bent or otherwise deformed duringelectromagnetic radiation propagation. This can be useful for a varietyof purposes, one of which is increased sensitivity in a sensor. Where asensor is sensitive to changes in a surface of a waveguide or claddingthat occur upon exposure to an analyte, as described above, sensitivitycan be increased as follows. The waveguide can be bent to its limit ofmaintaining total internal reflection, which is readily determined bybending the waveguide too far and then returning the waveguide to aconformation allowing total internal reflection. Where the interactionof an analyte with the waveguide decreases the difference in refractiveindex between waveguide and cladding, loss of electromagnetic radiationpassing through the waveguide can be indicative of interaction with ananalyte, and is made much more sensitive where the waveguide is almostat the limit of maintaining total internal reflection prior to exposureto the analyte. In another example, where coupling between waveguides ishighly dependent upon the conformation of the waveguides, altering theconformation of the waveguides (facilitated with a flexible substrate)can result in operation very near the limits of coupling where exposureto an analyte will relatively more greatly affect coupling.

Referring now to FIG. 20, an array 286 of waveguides 288, 290, 292, 294and 296, which are essentially linear and parallel, is illustrated.Where the array is fabricated such that conditions allow couplingbetween waveguides, as described above, light introduced into waveguide292 can couple into waveguides 290 and 294, and from waveguide 290 cancouple back into waveguide 292 and into waveguide 288, and fromwaveguide 294 can couple back into waveguide 292 and into waveguide 296.The result is that an interferometer is created and an interferencepattern defined by radiation emerging from each of waveguides 288-296 iscreated and is distinctive based upon spacing of the waveguides,refractive index difference between waveguide and cladding, waveguidedimensions, wavelength of radiation, and propagation length. The systemof FIG. 20 can serve as a sensor since any change in refractive indexdiffers at the boundaries of one or more waveguides, for example adifference in refractive index of the cladding surrounding waveguides288-296 such as via exposure to an electric field or electromagneticradiation, exposure to a fluid, or exposure to another analyte asdescribed above will alter the interference pattern emerging fromwaveguides 288-296.

A series of working examples were conducted relating to waveguides. Withthe exception of cross-linking of the polymer, synthesis was conductedin a class-100 clean room. A poly(dimethylsiloxane) (PDMS) elastomericmold, or applicator, 20 (sylgard 184, Dow Corning, Silicone Elastomer:curing agent=15:1) was cast from a photoresist pattern made in astandard photolithographic process (Kumar, et al., Langmuir, 10, 1498(1994)). With reference to FIG. 15, an array of waveguides 38 was formedby filling the relief structure (indentations 24) in applicator surface22 of applicator 20 with a liquid prepolymer (polyurethane, NOA-73,Norland Products New Brunswick, N.J.) and then placing the applicatorsurface of the filled applicator 20 on substrate surface 28 of a Si(100)wafer 30 supporting a 2 micron-thick layer of SiO₂. The prepolymer wascross-linked in situ by irradiating the system for 1 hour at a distanceof 1 centimeter with a 450 W medium-pressure Hg vapor lamp (type7825-34, Ace Glass, Vineland, N.J.). After UV exposure, the elastomericmold (applicator 20) was peeled away, leaving an array of waveguidestructures 38 on substrate 30. The technique was pattern used togenerate waveguides with a variety of widths of 2.0, 2.6, 3.0, and 4.0microns, and spacings of 2.0, 4.0, and 8.0 microns. All waveguides hadthe same height of approximately 1 micron. The length of the waveguideswas determined by the points at which the wafer was fractured. In oneset of embodiments the waveguide array was left unclad. In embodimentsin which cladding was applied, cladding was made by providing a thicklayer of the same liquid prepolymer and applying it to the waveguides,the surfaces of which had been slightly oxidized by exposure for about10 minutes in a UV-ozone cleaner (models 13550 and 13550-2, BoekelIndustries) to render them hydrophilic and improve adhesion. The systemwas heated to 85° C. on a hot plate to decrease the viscosity of theprepolymer, and the excess prepolymer was allowed to drain to one edge.The thin layer of prepolymer left on the surface was looselycross-linked by brief (1 minute) exposure to UV light (365 nm) from a 4W hand-held lamp (Blak-Ray UV lamp model UVL-21, UVP, San Gabrielle,Calif.). The ends of the clad waveguides were squared by cleaving thesubstrate. After cleaving, the cladding was cured completely (30seconds) with the 450 W medium-pressure Hg vapor lamp. This procedureallowed the ends of the waveguides to be cleaved when the cladding layerwas in the liquid phase, preventing the cladding from de-adhering fromthe guides.

FIG. 21 is a photocopy of an SEM image of an unclad waveguide array, andFIG. 22 is a photocopy of an SEM image of a clad array, each fabricatedaccording to this technique. In each case waveguide width was about 2.6microns, waveguide spacing was about 2.0 microns, and waveguide heightwas about 1.0 microns.

FIG. 23 is a schematic diagram of apparatus used to couple light intoand out of waveguide arrays fabricated as described immediately above.Light from a He-Ne laser 298 (633 nm) was first coupled into asingle-mode optical fiber 300 which was butt-coupled to the end ofwaveguides of array 302 (representative of a variety of waveguide arraysfabricated as described immediately above, and tested in accordance withthis example) using a precision 3-dimensional translation stage 304.Light also could be coupled into the waveguide array using focusingapparatus. That is, light from a laser could be focused, through a lensarrangement, to the end of waveguides of the array 302. Using thisapparatus, light was selectively coupled into individual waveguides inthe array, or into the cladding between or above the waveguides. Theoutput light from the waveguides was imaged with a microscope objective305 and recorded on a CCD camera 306. The shapes and intensities of theoutputs of the individual waveguides could easily be observed (in theabsence of the objective 305 the far field patterns from adjacentwaveguides overlapped).

FIGS. 24a-g show the results of a variety of different waveguide arraysand inputs, and demonstrate tailorable coupling, using the apparatus ofFIG. 23 and waveguide arrays fabricated as described above. In FIG. 24a,trapezoidal waveguides 38 indicate the positions, in cross-section, of 3micron-wide waveguides with neighboring waveguides separated by 8microns. The height of each waveguide was 1 micron. Optical fiber 300was positioned as indicated, in alignment with the central of the 5waveguides. FIG. 24b is a photocopy of a CCD camera frame grab of theoutput of the system of FIG. 24a. A single-mode output occurred, with noevanescent coupling between adjacent waveguides. FIG. 24c isrepresentative of a second waveguide structure fabricated in accordancewith the technique described above, with waveguides separated by 4microns, rather than 8 microns. The UV exposure time for the array ofFIG. 24c was the same as for the array of FIG. 24a. However, the 4micron spacing was small enough to allow evanescent coupling betweenguides and light was observed in 5 adjacent waveguides (FIG. 24d;photocopy of a CCD camera frame grab of result). Additionally, as theinput optical fiber was moved to adjacent waveguides, this outputpattern moved in register. The reproducibility and symmetry of thepattern established the uniformity of the coupling between thewaveguides in the array. The low level of light at the exit of thecentral waveguide was caused by efficient coupling of light from thecentral waveguide into adjacent waveguides.

FIG. 24e demonstrates the ability to modify the coupling betweenadjacent waveguides by controlling the difference in refractive indicesbetween the guides and their cladding by manipulating exposure timeduring UV curing. FIG. 24e is a photocopy of a CCD camera frame grab ofoutput of the waveguide of FIG. 24c (which produced the pattern of FIG.24d) after additional exposure of the array (waveguides plus cladding)under the 450 W medium-pressure Hg vapor lamp. This exposure reduced theindex difference between waveguide core and cladding, and increased thecoupling between the waveguides. The change is most easily seen in thechange in brightness of the center waveguide between FIG. 24d and FIG.24e. In FIG. 24d, the light coupled out of the center waveguide into theadjacent waveguides. In FIG. 24e, the light coupled from the adjacentwaveguides back into the center waveguide. Thus, the center waveguidesformed an interferometer. Light from the single waveguide directlyaddressed by optic fiber 300 was evanescently coupled into ninewaveguides and many closed-path interferometers were formed.

FIG. 24g shows the output of the array when light was coupled intocladding between the waveguides as shown in FIG. 24f. No waveguideoutput was observed and very little light was observed from the outputof the cladding. This demonstrated that the excitation of multiplewaveguides as shown in FIGS. 12d-e was the result of coupling frompropagating waveguide mode to propagating waveguide mode, not fromcladding modes to waveguide modes. This interpretation was supported bynumerical simulations.

Two-micron-high clad waveguides of width 2.0, 2.6, 3.0, and 4.0 micronsand spacing of 2, 4, and 8 microns were fabricated. These tallerwaveguides had cross-sections approximately equal to the 3.3 micron modediameter of the optical fiber 300, and gave a coupling efficiency ofapproximately 35% for a 6 millimeter-long waveguide. Propagation losswas measured in these waveguides to be less than 0.6 dB/cm, which is thelimit of measurement uncertainty in the system used.

To demonstrate essentially instantaneous formation of plural waveguidearrays, a waveguide fabrication technique was carried out as describedabove. An array of about 1,000 3-centimeter-long, two-micron-wide,one-micron-high waveguides were formed over a 0.8 by 3 square centimeterarea in a single step taking only five minutes. The parallelism of thisprocedure makes it a tremendously useful technique for the fabricationof complex but low-cost integrated optical devices.

FIG. 25 illustrates another embodiment of the invention for formation ofa structure on a substrate surface using a forming article. In thetechnique illustrated, fluid precursor 36 is first placed on substratesurface 28, then forming article 20 is brought into contact with fluidprecursor 36 and pressed against substrate surface 28 such that thecontact surface 26 of the article seals portions of surface 28 that itcontacts, thereby forming channels, defined by indentations and portionsof substrate surface 28 not contacted by contact surface 26 of theforming article. This is another embodiment in which a micromold iscreated, defined by article 20 and substrate surface 28. In FIG. 25,following hardening of fluid precursor 36 to the point that it isessentially self-supporting (if it is not so hardened prior to formingwith article 20), the applicator is removed resulting in structure 38which, depending upon the material selected, can be further cured orsintered and which may shrink in the process.

In the working examples described below, a drop of fluid precursor 36(referring to FIG. 25), was placed on a freshly cleaned substrate andthen article 28 was placed face down upon the substrate. A pressure ofroughly 10 psi was applied. The area of the patterned surface wastypically 1-5 cm² with feature sizes in the micron range. Liquiddewetting of the surface upon application of the applicator was carriedout to allow contact of the contact surface 26 of article 20 and thesubstrate in regions where no fluid precursor derived material wasdesired. Dewetting is driven by both applied pressure and difference ofinterfacial tension between fluid precursor 36 and contact surface 26 ofarticle 20. More precisely, the dewetting speed is proportional to Swhere S=γ_(LS)+γ_(LE)−γ_(SE); γ_(LS) is the liquid-substrate interfacialtension, γ_(LE) is the liquid-elastomer interfacial tension and γ_(SE)is the substrate-elastomer interfacial tension. (F. Brochard-Wyart, P.-G. de Gennes, J. Phys.: Condens. Matter, 1994, 6, A9). Since γ_(SE) isFixed, the interfacial tension of the fluid precursor solution wasincreased in order to accelerate dewetting. Although pressure improvesthe definition of features, it cannot be increased too much because ofthe deformations induced in the mold if deformation is not required.Diluting fluid precursor with a suitable solvent (in the workingexamples, acetonitrile, a polar solvent with low viscosity and highsurface tension that does not swell the mold) allowed satisfactorydewetting for all patterns used.

Gelation occurred within about an hour, although the mold and structurewere allowed to remain undisturbed for about 12 h to allow reasonableconsolidation. Gelling time can, however, be decreased by raising pH ofthe precursor to about 4-5 before casting, and some structures wereproduced in less than 30 minutes using this technique.

Working examples of molding of sol-gel fluid precursors using a formingarticle of the invention were carried out. In this set of examples,silicon wafers (Silicon Sense, Massachusetts) were cleaned briefly in anoxygen plasma cleaner before use. Tetramethyl-orthosilicate anddi-sec-butoxyaluminoxytriethoxysilane (United Chemicals), titaniumisopropoxide and boron triethoxide (Aldrich), oxalic acid andacetonitrile (Fisher) were used as received.

Patterned Solid: A silica sol-gel precursor was molded against a siliconwafer that had been patterned by anisotropic etching with squarepyramidal pits. A 50-nm thick gold film was prepared on a <100> siliconwafer primed with 2 nm of titanium by e-beam evaporation. A monolayer ofhexadecanethiolate was patterned on the wafer using microcontactprinting so that the resulting pattern presented uncovered 2-μm squares,and the unprotected gold was removed with a cyanide etch. (A. Kumar, G.M. Whitesides, Applied Physics Letters 1993, 63, 2002). The nativesilica oxide layer was then removed by etching in 2% HF for 30 sec. Thesilicon was etched in a 40% by weight solution of KOH in water andisopropanol; this anisotropic etch generated pyramidal pits. Theremaining gold was removed with aqua regia. The surface of the resultingtextured solid was treated by putting the wafer under static vacuum witha drop of (tridecafluoro-1,1,2,2-tetrahydro-octyl)-1-trichlorosilane for30 min. This compound polymerized on the surface and made a layer thatreduced adhesion to the surface.

A mixture of 6.5 g TMOS and 1.5 g of water acidified to pH=1 by addingoxalic acid was stirred for 1 min and left at room temperature for 1 h(sol A). The mold was prepared by putting a 1 cm² piece of the texturedwafer in a plastic petri dish. Just before casting in the mold, 5 dropsof aqueous ammonia (pH=11) were added to 3 g of sol A. The wafer wascovered with 0.5 ml of this solution. The preparation was then placed ina closed 100 cm³ container for 24 h. The solid structure was notadhering to the mold at this point and was carefully removed. It wasthen dried slowly at room temperature for a week, then at 60° C. for 2days. It was finally annealed at 1100° C. for 10 h.

The resulting array of silica pyramids prepared by this technique wasanalyzed via SEM. The radius of curvature at the tips of the pyramidswas less than 50 nm and the angle of the side of the pyramid was 54-58°.This value is compatible with that obtained with this type of siliconetching. (Barycka, et al., Sensors and Actuators, 1995, A48, 229). Thisdemonstrates that shrinkage taking place during annealing is essentiallyisotropic. The sol-gel precursor was molded against a Si/SiO₂ waferwhose surface had been passivated by silanization. The structure wasannealed at 1100° C. It measured 5×5×0.3 mm.

Optical waveguides of doped silica on Si/SiO₂ were formed. The silicawas doped with aluminum oxide in order to increase its refractive index.Low scattering by the edges of the waveguides can be achieved by anannealing step at a temperature where the viscosity is low enough toallow relaxation of the roughness. In the second working exampledescribed below, this temperature was reduced by adding boron oxide tothe silica.

Specifically, 0.5 g of di-sec-butoxyaluminoxytriethoxysilane was addedto 3 g of sol A. After stirring for 6 h, 3 g of acetonitrile were addedto the clear solution (sol B). A solution of 0.8 g of trimethylborate in3 g of acetonitrile was added to 3 g of sol A and left at roomtemperature for 1 h (sol C).

One drop of the solution (sol B or C) was placed on a freshly cleanedsilicon wafer bearing a 2-μm thick thermal oxide layer. A 1-cm²elastomeric forming article having a protrusion pattern complementary tothe final pattern of the waveguide (illustrated schematically in FIG.25) was immediately pressed against the surface. The whole structure wasplaced in a closed 100-cm³ container with one drop of aqueous ammonia(30%). After 18 h, the mold was removed and the structure wasconsolidated by annealing for 3 h at 1100° C. (for sol B) and 15 min at800° C. or 900° C. (for sol C).

FIGS. 26-29 are photocopies of SEM images of waveguides produced inaccordance with this aspect of the invention. FIG. 26 is a photocopy ofan SEM image of an aluminosilicate waveguide. FIGS. 27 and 29 arephotocopies of SEM images of borosilicate waveguides. FIGS. 27 and 28show borosilicate lines at different stages of sintering: FIG. 27 showsborosilicate lines after annealing at 800° C. for 10 minutes. FIG. 28shows the lines after annealing at 900° C. for 10 minutes. Whereas puresintering seemed to occur at 800° C., the cross section of the lineschanged dramatically after annealing at 900° C., due to the melting ofthe glass, resulting in smoother edges. The composition of the glass wasfound by XPS to be 9% B₂O₃ and 91% SiO₂. The waveguiding behavior of thealuminosilicate lines was characterized by coupling a 633-nanometerlight beam into one end of a 5 mm long line and imaging the other end.The lines appeared to be single mode waveguides with slight couplingbetween adjacent lines.

Described above are a variety of sensors of biological or chemicalmolecules, or the like, that can be made using waveguides fabricated inaccordance with the invention. In another set of embodiments, sensors ofdisplacement can be provided. For example, with reference to FIG. 24,where the waveguide array is subjected to compression or tensile forcesin a direction perpendicular to the waveguides, causing the waveguidesto move closer to or farther apart from each other, coupling betweenwaveguides will change detectably. This can serve as a displacementsensor, pressure sensor, tension sensor, or the like. The waveguidearray can be arranged to sense a force by being bent, for example tosense a force applied to an edge of the waveguide, and when thewaveguide is bent spacing between waveguides will change and thecoupling pattern will change. Waveguides made of glass as describedabove may also serve as active devices for integrated optics. Forinstance, aluminosilicate waveguides can be doped with rare earth, likeneodymium or erbium. Doped waveguides can be used as integratedlight-amplifiers or lasers when placed in a suitably geometry. A regulararray of doped waveguides fabricated by this method, when put in aresonant cavity, could exhibit a very interesting behavior where all thelasers would be in phase, leading to a much higher intensity light beam.

What is claimed is:
 1. A method of creating a pattern of a species at adefined region proximate a substrate surface, comprising: providing anarticle having a contoured surface including at least one indentationdefining a pattern; forming at a first region proximate a substratesurface, in a pattern corresponding to the indentation pattern, a fluidprecursor of the species; and allowing the fluid precursor, comprising asolution or suspension of an inorganic compound, to harden at the firstregion of the substrate surface, in a pattern corresponding to theindentation pattern and in an area including a portion having a lateraldimension of less than about 1 mm, while leaving a second regionproximate the substrate surface, contiguous with the first region, freeof the species.
 2. A method as in claim 1, wherein the fluid precursorcomprises a suspension of particles in a fluid carrier and the allowingstep comprises allowing the fluid carrier to dissipate therebydepositing the particles at the first region of the substrate surface.3. A method as in claim 2, wherein the particles are microbeads.
 4. Amethod as in claim 1, wherein the fluid precursor comprises a chemicallyactive agent that is capable of promoting deposition of a metal.
 5. Amethod as in claim 1, wherein the fluid precursor is a prepolymericspecies, and the forming step comprises positioning the contouredsurface of the article proximate the substrate surface thereby creatinga channel defined by the at least one indentation and the first regionof the substrate surface and allowing the prepolymeric species to flowinto the channel via capillary action, and the allowing step comprisesforming a polymeric article from the prepolymeric species.
 6. A methodas in claim 5, wherein the allowing step comprises allowing theprepolymeric species to form a polymeric article in an area including aportion having a lateral dimension of less than about 500 microns.
 7. Amethod of promoting a chemical reaction at a defined region proximate asubstrate surface, comprising: positioning an article proximate asubstrate surface and applying, to a first region proximate thesubstrate surface via capillary action involving the article, achemically active agent; and allowing a chemical reaction involving thechemically active agent to take place at the first region proximate thesubstrate surface.
 8. A method as in claim 7, wherein the chemicallyactive agent is a prepolymeric species and the allowing step comprisesforming a polymeric article from the prepolymeric species.
 9. A methodas in claim 7, wherein the chemically active agent is coupled to aparticulate carrier that is applied, in a fluid carrier via capillaryaction involving the article, to the first region proximate thesubstrate surface.
 10. A method as in claim 9, wherein the particulatecarrier comprises microbeads.
 11. A method as in claim 7, the allowingstep comprising allowing a chemical reaction to take place at the firstregion in an area including a portion having a lateral dimension of lessthan about one millimeter.
 12. A method as in claim 11, the allowingstep comprising allowing a chemical reaction to take place at the firstregion in an area including a portion having a lateral dimension of lessthan about 500 microns.
 13. A method as in claim 12, wherein theallowing step comprises allowing a chemical reaction to take place atthe first region in an area including a portion having a lateraldimension of less than about 100 microns.
 14. A method as in claim 13,the allowing step comprising allowing a chemical reaction to take placeat the first region in an area including a portion having a lateraldimension of less than about 50 microns.
 15. A method as in claim 14,the allowing step comprising allowing a chemical reaction to take placeat the first region in an area including a portion having a lateraldimension of less than about 20 microns.
 16. A method as in claim 7,wherein the chemically active agent is a prepolymeric species and theallowing step comprises allowing the prepolymeric species to form apolymeric article at the first region in an area including a portionhaving a lateral dimension of less than about one millimeter.
 17. Amethod as in claim 16, wherein the allowing step comprises allowing theprepolymeric species to form a polymeric article at the first region inan area including a portion having a lateral dimension of less thanabout 500 microns.
 18. A method as in claim 7, the positioning stepcomprising positioning an article having a contoured surface includingat least one indentation defining a pattern with the contoured surfaceproximate the substrate surface so as to form a channel defined by theat least one indentation and the first region and allowing thechemically active agent to enter the channel via capillary action so asto be positioned proximate the first region.
 19. A method of creating apattern of a species at a defined region proximate a substrate surfacecomprising: positioning a forming article proximate a substrate surfaceand applying, to a first region proximate the substrate surface viacapillary action involving the article, a fluid precursor of thespecies; allowing the fluid precursor to harden to the extent that thespecies is self-supporting at the first region proximate the substratesurface; and removing the forming article from the substrate surface.20. A method of creating a pattern of a species at a defined regionproximate a substrate surface, comprising: providing an article having acontoured surface including at least one indentation defining a pattern;transferring a fluid precursor of the species from the contoured surfaceof the article to a first region proximate a substrate surface to format the first region, in a pattern corresponding to the indentationpattern, a fluid precursor of the species; allowing the fluid precursorto harden at the first region of the substrate surface, in a patterncorresponding to the indentation pattern, while leaving a second regionproximate the substrate surface, contiguous with the first region, freeof the species; and then removing the article from the substratesurface.
 21. A method as in claim 1, wherein the fluid precursor is aprecursor of a reactive ion etch mask.
 22. A method as in claim 21, theallowing step including allowing the fluid precursor to harden and toform a reactive ion etch mask at the first region of the substratesurface, the method further comprising exposing the substrate toreactive ion etch conditions and allowing at least a portion of thesubstrate surface at the second region to be etched by reactive ionetching.
 23. A method comprising: providing an article having acontoured surface including at least one indentation defining a pattern;forming at a first region proximate a substrate surface, in a patterncorresponding to the indentation pattern, a fluid precursor of areactive ion etch mask; and allowing the fluid precursor to harden toform a reactive ion etch mask at the first region of the substratesurface while leaving a second region proximate the substrate surface,contiguous with the first region, free of the species.
 24. A method asin claim 23, involving allowing the fluid precursor to harden to form areactive ion etch mask at the first region of the substrate surface in apattern corresponding to the indentation pattern and in an areaincluding a portion having a lateral dimension of less than about 1 mm.25. A method as in claim 23, comprising forming the fluid precursor inthe pattern on the surface by providing an amount of the fluid precursoron the substrate surface and pressing the contoured surface of thearticle into the precursor against the substrate surface.
 26. A methodas in claim 23, further comprising exposing the substrate to reactiveion etch conditions and allowing at least a portion of the substratesurface at the second region to be etched by reactive ion etching.
 27. Amethod as in claim 23, wherein the surface is nonplanar.
 28. A method asin claim 1, wherein the forming step comprises applying a vacuum in achannel, defined by the at least one indentation and the first region,to urge the fluid processor to flow therein.